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Exploring the interaction between the gut microbiota and cyclic adenosine monophosphate-protein kinase A signaling pathway:a potential therapeutic approach for neurodegenerative diseases
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作者 Fengcheng Deng Dan Yang +6 位作者 Lingxi Qing Yifei Chen Jilian Zou Meiling Jia Qian Wang Runda Jiang Lihua Huang 《Neural Regeneration Research》 SCIE CAS 2025年第11期3095-3112,共18页
The interaction between the gut microbiota and cyclic adenosine monophosphate(cAMP)-protein kinase A(PKA)signaling pathway in the host's central nervous system plays a crucial role in neurological diseases and enh... The interaction between the gut microbiota and cyclic adenosine monophosphate(cAMP)-protein kinase A(PKA)signaling pathway in the host's central nervous system plays a crucial role in neurological diseases and enhances communication along the gut–brain axis.The gut microbiota influences the cAMP-PKA signaling pathway through its metabolites,which activates the vagus nerve and modulates the immune and neuroendocrine systems.Conversely,alterations in the cAMP-PKA signaling pathway can affect the composition of the gut microbiota,creating a dynamic network of microbial-host interactions.This reciprocal regulation affects neurodevelopment,neurotransmitter control,and behavioral traits,thus playing a role in the modulation of neurological diseases.The coordinated activity of the gut microbiota and the cAMP-PKA signaling pathway regulates processes such as amyloid-β protein aggregation,mitochondrial dysfunction,abnormal energy metabolism,microglial activation,oxidative stress,and neurotransmitter release,which collectively influence the onset and progression of neurological diseases.This study explores the complex interplay between the gut microbiota and cAMP-PKA signaling pathway,along with its implications for potential therapeutic interventions in neurological diseases.Recent pharmacological research has shown that restoring the balance between gut flora and cAMP-PKA signaling pathway may improve outcomes in neurodegenerative diseases and emotional disorders.This can be achieved through various methods such as dietary modifications,probiotic supplements,Chinese herbal extracts,combinations of Chinese herbs,and innovative dosage forms.These findings suggest that regulating the gut microbiota and cAMP-PKA signaling pathway may provide valuable evidence for developing novel therapeutic approaches for neurodegenerative diseases. 展开更多
关键词 cyclic adenosine monophosphate emotional disorders gut microbiota neurodegenerative diseases neurological diseases protein kinase A reciprocal regulation signaling pathway STRATEGY THERAPIES
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RGS4 promotes the progression of gastric cancer through the focal adhesion kinase/phosphatidyl-inositol-3-kinase/protein kinase B pathway and epithelial-mesenchymal transition
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作者 Peng-Yu Chen Pei-Yao Wang +7 位作者 Bang Liu Yang-Pu Jia Zhao-Xiong Zhang Xin Liu Dao-Han Wang Yong-Jia Yan Wei-Hua Fu Feng Zhu 《World Journal of Gastroenterology》 SCIE CAS 2025年第2期113-127,共15页
BACKGROUND Regulator of G protein signaling(RGS)proteins participate in tumor formation and metastasis by acting on theα-subunit of heterotrimeric G proteins.The speci-fic effect of RGS,particularly RGS4,on the progr... BACKGROUND Regulator of G protein signaling(RGS)proteins participate in tumor formation and metastasis by acting on theα-subunit of heterotrimeric G proteins.The speci-fic effect of RGS,particularly RGS4,on the progression of gastric cancer(GC)is not yet clear.AIM To explore the role and underlying mechanisms of action of RGS4 in GC develop-ment.METHODS The prognostic significance of RGS4 in GC was analyzed using bioinformatics based public databases and verified by immunohistochemistry and quantitative polymerase chain reaction in 90 patients with GC.Function assays were employed to assess the carcinogenic impact of RGS4,and the mechanism of its possible influence was detected by western blot analysis.A nude mouse xenograft model was established to study the effects of RGS4 on GC growth in vitro.RESULTS RGS4 was highly expressed in GC tissues compared with matched adjacent normal tissues.Elevated RGS4 expression was correlated with increased tumor-node-metastasis stage,increased tumor grade as well as poorer overall survival in patients with GC.Cell experiments demonstrated that RGS4 knockdown suppressed GC cell proliferation,migration and invasion.Similarly,xenograft experiments confirmed that RGS4 silencing significantly inhibited tumor growth.Moreover,RGS4 knockdown resulted in reduced phosphorylation levels of focal adhesion kinase,phosphatidyl-inositol-3-kinase,and protein kinase B,decreased vimentin and N-cadherin,and elevated E-cadherin.CONCLUSION High RGS4 expression in GC indicates a worse prognosis and RGS4 is a prognostic marker.RGS4 influences tumor progression via the focal adhesion kinase/phosphatidyl-inositol-3-kinase/protein kinase B pathway and epithelial-mesenchymal transition. 展开更多
关键词 Gastric cancer PROGNOSIS Regulator of G protein signaling 4 Focal adhesion kinase Epithelial-mesenchymal transition
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Involvement of Calcium dependent Protein Kinases in ABA regulation of Stomatal Movement 被引量:9
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作者 王喜庆 武维华 《Acta Botanica Sinica》 CSCD 1999年第5期556-559,共4页
Patch clamp techniques were employed to investigate if calcium dependent protein kinases (CDPKs) be involved in the signal transduction pathways of stomatal movement regulation by the phytohormone abscisic acid (ABA... Patch clamp techniques were employed to investigate if calcium dependent protein kinases (CDPKs) be involved in the signal transduction pathways of stomatal movement regulation by the phytohormone abscisic acid (ABA) in Vicia faba. Stomatal opening was completely inhibited by external application of 1 μmol/L ABA, and such ABA inhibition was significantly reversed by the addition of CDPK inhibitor trifluoperazine (TFP). The inward whole cell K + currents were inhibited by 60% in the presence of 1 μmol/L intracellular ABA, and this inhibition was completely abolished by the addition of CDPK competitive substrate histone Ⅲ S. The results suggest that CDPKs may be involved in the signal transduction cascades of ABA regulated stomatal movements. 展开更多
关键词 Calcium dependent protein kinases (CDPKs) K + channels Abscisic acid Stomatal guard cells
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N-methyl-D-aspartate receptors mediate diphosphorylation of extracellular signal-regulated kinases through Src family tyrosine kinases and Ca^2+/calmodulin-dependent protein kinase Ⅱ in rat hippocampus after cerebral ischemia 被引量:7
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作者 吴辉文 李洪福 郭军 《Neuroscience Bulletin》 SCIE CAS CSCD 2007年第2期107-112,共6页
Objective: Extracellular signal-regulated kinases (ERKs) can be activated by calcium signals. In this study, we investigated whether calcium-dependent kinases were involved in ERKs cascade activation after global c... Objective: Extracellular signal-regulated kinases (ERKs) can be activated by calcium signals. In this study, we investigated whether calcium-dependent kinases were involved in ERKs cascade activation after global cerebral ischemia. Methods Cerebral ischemia was induced by four-vessel occlusion, and the calcium-dependent proteins were detected by immunoblot. Results Lethal-simulated ischemia significantly resulted in ERKs activation in N-methyl-D-aspartate (NMDA) receptor-dependent manner, accompanying with differential upregulation of Src kinase and Ca^2+/calmodulin-dependent protein kinase Ⅱ (CaMKⅡ) activities. With the inhibition of Src family tyrosine kinases or CaMKⅡ by administration of PP2 or KN62, the phosphorylation of ERKs was impaired dramatically during post-ischemia recovery. However, ischemic challenge also repressed ERKs activity when Src kinase was excessively activated. Conclusions Src family tyrosine kinases and CaMKⅡ might be involved in the activation of ERKs mediated by NMDA receptor in response to acute ischemic stimuli in vivo, but the intense activation of Src kinase resulted from ischemia may play a reverse role in the ERKs cascade. 展开更多
关键词 cerebral ischemia extracellular signal-regulated kinases NMDA receptors Src family tyrosine kinases CaMKⅡ
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Caffeic acid phenethyl ester up-regulates antioxidant levels in hepatic stellate cell line T6 via an Nrf2-mediated mitogen activated protein kinases pathway 被引量:12
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作者 Ning Yang Juan-Juan Shi +6 位作者 Feng-Ping Wu Mei Li Xin Zhang Ya-Ping Li Song Zhai Xiao-Li Jia Shuang-Suo Dang 《World Journal of Gastroenterology》 SCIE CAS 2017年第7期1203-1214,共12页
AIM To investigate the antioxidant effect of caffeic acid phenethyl ester (CAPE) in hepatic stellate cell-T6 (HSC-T6) cells cultured in vitro and the potential mechanisms. METHODS HSC-T6 cells were cultured in vitro a... AIM To investigate the antioxidant effect of caffeic acid phenethyl ester (CAPE) in hepatic stellate cell-T6 (HSC-T6) cells cultured in vitro and the potential mechanisms. METHODS HSC-T6 cells were cultured in vitro and treated with various concentrations of CAPE for 24, 48 and 72 h, respectively. Cell proliferation was investigated using the MTT assay, and cell ultrastructural alterations were observed by transmission electron microscopy. Flow cytometry was employed to investigate the effects of CAPE on apoptosis and the levels of reactive oxygen species in HSC-T6 cells cultured in vitro. An enzyme immunoassay instrument was used to evaluate antioxidant enzyme expression. The effect on alpha-smooth muscle actin was shown using immunofluorescence. Gene and protein levels of Nrf2, related factors, and mitogen activated protein kinases (MAPKs), in HSC-T6 cells were detected using RT-PCR and Western blot, respectively. RESULTS CAPE inhibited the proliferation and activation of HSC-T6 cells cultured in vitro. CAPE increased the antioxidant levels and the translocation of Nrf2 from the cytoplasm to the nucleus in HSC-T6 cells. Moreover, the phosphorylation of MAPKs in cells decreased in response to CAPE. Interestingly, CAPE-induced oxidative stress in the cells was significantly attenuated by pretreatment with MAPKs inhibitors. CONCLUSION CAPE inhibits cell proliferation and up-regulates the antioxidant levels in HSC-T6 cells partly through the Nrf2-MAPKs signaling pathway. 展开更多
关键词 Caffeic acid phenethyl ester Liver fibrosis ANTIOXIDATION Nrf2 Mitogen activated protein kinases
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Downregulation of cold-inducible RNA-binding protein activates mitogen-activated protein kinases and impairs spermatoRenic function in mouse testes 被引量:8
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作者 Zhi-Ping Xia Xin-Min Zheng +3 位作者 Hang Zheng Xiao-Jun Liu Gui-Yong Liu Xing-Huan Wang 《Asian Journal of Andrology》 SCIE CAS CSCD 2012年第6期884-889,共6页
Cold-inducible RNA-binding protein (CIRP) is an RNA-binding protein that is expressed in normal testes and downregulated after heat stress caused by cryptorchidism, varicocele or environmental temperatures. The purp... Cold-inducible RNA-binding protein (CIRP) is an RNA-binding protein that is expressed in normal testes and downregulated after heat stress caused by cryptorchidism, varicocele or environmental temperatures. The purpose of this study was to investigate the functions of CIRP in the testes. We employed RNAi technique to knock down the expression of CIRP in the testes, and performed haematoxylin and eosin staining to evaluate morphological changes following knockdown. Germ cell apoptosis was examined by terminal deoxynucleotidal transferase-mediated dUTP nick end labelling (TUNEL) assay, and mitogen-activated protein kinase (MAPK) signalling pathways were investigated by Western blotting to determine the possible mechanism of apoptosis. We found that using siRNA is a feasible and reliable method for knocking down gene expression in the testes. Compared to controls, the mean seminiferous tubule diameter (MSTD) and the thickness of the germ cell layers decreased following siRNA treatment, whereas the percentage of apoptotic seminiferous tubules increased. The p44/p42, p38 and SAPK/JNK MAPK pathways were activated after downregulation of CIRP. In conclusion, we discovered that downregulation of CIRP resulted in increased germ cell apoptosis, possibly viathe activation of the p44/p42, p38 and SAPK/JNK MAPK pathways. 展开更多
关键词 cold-inducible RNA-binding protein (CIRP) mitogen-activated protein kinase (MAPK) siRNA in vivo SPERMATOGENESIS heat stress male infertility
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Evidence for a role of mitogen-activated protein kinases in the treatment of experimental acute pancreatitis 被引量:3
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作者 Natasha Irrera Alessandra Bitto +2 位作者 Monica Interdonato Francesco Squadrito Domenica Altavilla 《World Journal of Gastroenterology》 SCIE CAS 2014年第44期16535-16543,共9页
Acute pancreatitis(AP) is an inflammatory disease characterized by acute inflammation and necrosis of the pancreatic parenchyma. AP is often associated with organ failure, sepsis, and high mortality. The pathogenesis ... Acute pancreatitis(AP) is an inflammatory disease characterized by acute inflammation and necrosis of the pancreatic parenchyma. AP is often associated with organ failure, sepsis, and high mortality. The pathogenesis of AP is still not well understood. In recent years several papers have highlighted the cellular and molecular events of acute pancreatitis. Pancreatitis is initiated by activation of digestive enzymes within the acinar cells that are involved in autodigestion of the gland, followed by a massive infiltration of neutrophils and macrophages and release of inflammatory mediators, responsible for the local and systemic inflammatory response. The hallmark of AP is parenchymal cell necrosis that represents the cause of the high morbidity and mortality, so that new potential therapeutic approaches are indispensable for the treatment of patients at high risk of complications. However, not all factors that determine the onset and course of the disease have been explained. Aim of this article is to review the role of mitogen-activated protein kinases in pathogenesis of acute pancreatitis. 展开更多
关键词 Experimental acute pancreatitis Mitogen-activated protein kinases Mitogen-activated protein kinases inhibitors CYTOKINES CHOLECYSTOKININ CERULEIN
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Signaling mechanisms in alcoholic liver injury: Role of transcription factors, kinases and heat shock proteins 被引量:3
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作者 Pranoti Mandrekar 《World Journal of Gastroenterology》 SCIE CAS CSCD 2007年第37期4979-4985,共7页
Alcoholic liver injury comprises of interactions of various intracellular signaling events in the liver. Innate immune responses in the resident Kupffer cells of the liver, oxidative stress-induced activation of hepat... Alcoholic liver injury comprises of interactions of various intracellular signaling events in the liver. Innate immune responses in the resident Kupffer cells of the liver, oxidative stress-induced activation of hepatocytes, fibrotic events in liver stellate cells and activation of liver sinusoidal endothelial cells all contribute to alcoholic liver injury. The signaling mechanisms associated with alcoholic liver injury vary based on the cell type involved and the extent of alcohol consumption. In this review we will elucidate the oxidative stress and signaling pathways affected by alcohol in hepatocytes and Kupffer cells in the liver by alcohol. The toll-like receptors and their down-stream signaling events that play an important role in alcohol-induced inflammation will be discussed. Alcohol-induced alterations of various intracellular transcription factors such as NFKB, PPARs and AP-1, as well as MAPK kinases in hepatocytes and macrophages leading to induction of target genes that contribute to liver injury will be reviewed. Finally, we will discuss the significance of heat shock proteins as chaperones and their functional regulation in the liver that could provide new mechanistic insights into the contributions of stress-induced signaling mechanisms in alcoholic liver injury. 展开更多
关键词 TNFΑ Toll-like receptors NFKB Heat shockproteins Mitogen-activated protein kinases
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Arctigenin attenuates paraquat-induced human lung epithelial A549 cell injury by suppressing ROS/p38 mitogen-activated protein kinases-mediated apoptosis 被引量:3
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作者 Chao Liu Zhao-rui Sun +7 位作者 Meng-meng Wang Zhi-zhou Yang Wei Zhang Yi Ren Xiao-qin Han Rui Liu Quan Li Shi-nan Nie 《World Journal of Emergency Medicine》 SCIE CAS CSCD 2022年第5期373-378,共6页
BACKGROUND:Paraquat(PQ)-induced acute lung injury(ALI)and pulmonary fi brosis are common diseases with high mortality but without eff ective antidotes in emergency medicine.Our previous study has proved that arctigeni... BACKGROUND:Paraquat(PQ)-induced acute lung injury(ALI)and pulmonary fi brosis are common diseases with high mortality but without eff ective antidotes in emergency medicine.Our previous study has proved that arctigenin suppressed pulmonary fibrosis induced by PQ.We wondered whether arctigenin could also have a protective eff ect on PQ-induced ALI.METHODS:A PQ-induced A549 cell injury model was used,and the effect of arctigenin was determined by a cell counting kit-8(CCK-8)cell viability assay.In addition,terminal deoxynucleotidyl transferase(TdT)-mediated dUTP nick-end labelling(TUNEL)staining assays and mitochondrial membrane potential assays were performed to evaluate the level of cell apoptosis.The generation of reactive oxygen species(ROS)was refl ected by dihydroethidium(DHE)staining and a 2’,7’-dichlorodihy drofluorescein diacetate(DCFH-DA)assay.Moreover,immunoblotting studies were used to assess the expression of mitogen-activated protein kinases(MAPKs)and p38 MAPK.RESULTS:Arctigenin attenuated PQ-induced inhibition of A549 cell viability in a dose-dependent manner.Arctigenin also significantly reduced PQ-induced A549 cell apoptosis,as refl ected by the TUNEL assay and mitochondrial membrane potential assay,which may result from suppressed ROS/p38 MAPK signaling because we found that arctigenin dramatically suppressed ROS generation and p38 MAPK phosphorylation.CONCLUSION:Arctigenin could attenuate PQ-induced lung epithelial A549 cell injury in vitro by suppressing ROS/p38 MAPK-mediated cell apoptosis,and arctigenin might be considered a potential candidate drug for PQ-induced ALI. 展开更多
关键词 PARAQUAT A549 cells ARCTIGENIN Reactive oxygen species Mitogen-activated protein kinases Apoptosis
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Mechanism of Retinoic Acid and Mitogen-activated Protein Kinases Regulating Hyperoxia Lung Injury 被引量:3
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作者 李文斌 常立文 +5 位作者 容志惠 张谦慎 王华 汪鸿 刘春梅 刘伟 《Journal of Huazhong University of Science and Technology(Medical Sciences)》 SCIE CAS 2006年第2期178-181,共4页
To investigate the protective effect of retinoic acid (RA) on hyperoxic lung injury and the role of RA as a modulator on mitogen-activated protein kinases (MAPKs), gastation 21 d Sprague- Dawley (SD) fetuses (t... To investigate the protective effect of retinoic acid (RA) on hyperoxic lung injury and the role of RA as a modulator on mitogen-activated protein kinases (MAPKs), gastation 21 d Sprague- Dawley (SD) fetuses (term = 22 d) were delivered by hysterotomy. Within 12-24 h of birth, premature rat pups were randomly divided into 4 groups (n= 12 each) : air-exposed control group (group Ⅰ ) ; hyperoxia-exposed group ( group Ⅱ ), air-exposed plus RA group (group Ⅲ ), hyperoxia-exposed plus RA group (group Ⅳ). Group Ⅰ , Ⅲ were kept in room air, and group Ⅱ , Ⅳ were placed in 85 % oxygen. The pups in groups Ⅲ and Ⅳ were intraperitoneally injected with RA (500 μg/kg every day). All lung tissues of premature rat pups were collected at the 4th day after birth. Terminal transferase d-UTP nick end labeling (TUNEL) staining was used for the detection of cell apoptosis. The expression of PCNA was immunohistochemically detected. Western blot analysis was employed for the determination of phosphorylated and total nonphosphorylated ERKs, JNKs or p38. Our results showed that lungs from the pups exposed to hyperoxia for 4 d exhibited TUNEL-positive nuclei increased markedly throughout the parenchyma (P〈0.01), and decreased significantly after RA treatment (P〈0.01). The index of PCNA-positive cells was significantly decreased (P〈0.01), and was significantly increased by RA treatment (P〈0.01). The air-space size was significantly enlarged, secondary crests were markedly decreased in hyperoxia-exposed animals. RA treatment improved lung air spaces and secondary crests in air-exposed pups, hut had no effect on hyperoxia-exposure pups. Western blotting showed that the amounts of JNK, p38 and ERK proteins in hyperoxia-exposure or RA-treated lung tissues were same as those in untreated lung tissues (P〈0.05), whereas activation of these MAPKs was markedly altered by hyperoxia and RA. After hyperoxia exposure, p-ERK1/2, p-JNK1/2 and p-p38 were dramatically increased (P〈0.01), whereas p-JNK1/2 and p-p38 were markedly declined and p-ERK1/2 was further elevated by RA treatment (P〈0.01). It is concluded that RA could decrease cell apoptosis and stimulate cell proliferation under hyperoxic condition. The protection Of RA on hyperoxia-induced lung injury was related'to the regulation of MAP kinase activation. 展开更多
关键词 hyperoxia lung injury mitogen-activated protein kinases retinoic acid APOPTOSIS PROLIFERATION
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Ceramide from sphingomyelin hydrolysis differentially mediates mitogen-activated protein kinases (MAPKs) activation following cerebral ischemia in rat hippocampal CA1 subregion 被引量:3
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作者 Xian Sun 《The Journal of Biomedical Research》 CAS 2010年第2期132-137,共6页
Objective: To explore the role that ceramide plays in the activation of mitogen-activated protein kinases (MAPKs) during cerebral ischemia and reperfusion. Methods: Rats were subjected to ischemia by the fourvesse... Objective: To explore the role that ceramide plays in the activation of mitogen-activated protein kinases (MAPKs) during cerebral ischemia and reperfusion. Methods: Rats were subjected to ischemia by the fourvessel occlusion (4-VO) method. The sphingomyelinase inhibitor TPCK was administered to the CA1 subregion of the rat hippocampus before inducing ischemia. Western blot was used to examine the activity of extracellular- signal regulated kinase (ERK) and c-Jun N-terminal protein kinase (JNK) using antibodies against ERK, JNK and diphosphorylated ERK and JNK. Results: At lh reperfusion post-ischemia, JNK reached its peak activity while ERK was undergoing a sharp inactivation (P 〈 0.05). The level of diphosphorylated JNK was significantly reduced but the sharp inactivation of ERK was visibly reversed (P 〈 0.05) by the sphingomyelinase inhibitor. Conclusion: The ceramide signaling pathway is up-regulated through sphingomyelin hydrolysis in brain ischemia, promoting JNK activation and suppressing ERK activation, culminating in the ischemic lesion. 展开更多
关键词 CERAMIDE cerebral ischemia extracellular-signal regulated kinase c-Jun N-terminal protein kinase
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Potential of ginsenoside Rg1 to treat aplastic anemia via mitogen activated protein kinase pathway in cyclophosphamide-induced myelosuppression mouse model
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作者 See-Hyoung Park 《World Journal of Stem Cells》 SCIE 2024年第11期900-905,共6页
Aplastic anemia(AA)is a rare but serious condition in which the bone marrow fails to produce sufficient new blood cells,leading to fatigue,increased susceptibility to infection,and uncontrolled bleeding.In this editor... Aplastic anemia(AA)is a rare but serious condition in which the bone marrow fails to produce sufficient new blood cells,leading to fatigue,increased susceptibility to infection,and uncontrolled bleeding.In this editorial,we review and comment on an article by Wang et al published in 2024.This study aimed to evaluate the potential therapeutic benefits of ginsenoside Rg1 in AA,focusing on its protective effects and uncovering the underlying mechanisms.Cyclophosphamide(CTX)administration caused substantial damage to the structural integrity of the bone marrow and decreased the number of hematopoietic stem cells,thereby establishing an AA model.Compared with the AA group,ginsenoside Rg1 alleviated the effects of CTX by reducing apoptosis and inflammatory factors.Mechanistically,treatment with ginsenoside Rg1 significantly mitigated myelosuppression in mice by inhibiting the mitogen activated protein kinase signaling pathway.Thus,this study indicates that ginsenoside Rg1 could be effective in treating AA by reducing myelosuppression,primarily through its influence on the mitogen activated protein kinase signaling pathway.We expect that our review and comments will provide valuable insights for the scientific community related to this research and enhance the overall clarity of this article. 展开更多
关键词 Aplastic anemia CYCLOPHOSPHAMIDE Ginsenoside Rg1 Hematopoietic stem cells APOPTOSIS INFLAMMATION Mitogen activated protein kinase
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Effects of invigorating-spleen and anticancer prescription on extracellular signal-regulated kinase/mitogen-activated protein kinase signaling pathway in colon cancer mice model
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作者 Wei Wang Jing Wang +2 位作者 Xiu-Xiu Ren Hai-Long Yue Zheng Li 《World Journal of Gastrointestinal Oncology》 SCIE 2024年第11期4468-4476,共9页
BACKGROUND Colon cancer(CC)is one of the most common malignant tumors in the gastrointestinal system.Overall,CC had the third highest incidence but the second highest mortality rate globally in 2020.Nowadays,CC is mai... BACKGROUND Colon cancer(CC)is one of the most common malignant tumors in the gastrointestinal system.Overall,CC had the third highest incidence but the second highest mortality rate globally in 2020.Nowadays,CC is mainly treated with capecitabine chemotherapy regimen,supplemented by radiotherapy,immunotherapy and targeted therapy,but there are still limitations,so Chinese medicine plays an important role.AIM To investigate the effects of invigorating-spleen and anticancer prescription(ISAP)on body weight,tumor inhibition rate and expression levels of proteins in extracellular-signal-regulated kinase(ERK)/mitogen-activated protein kinase(MAPK)signaling pathway in CC mice model.METHODS The CC mice model were established and the mice were randomly divided into 5 groups,including the control group,capecitabine group,the low-dose,mediumdose and high-dose groups of ISAP,with 8 mice in each group,respectively.After 2 weeks of intervention,the body weight and tumor inhibition rate of mice were observed,and the expression of RAS,ERK,phosphorylated ERK(p-ERK),C-MYC and matrix metalloproteinase 2(MMP2)proteins in the tissues of tumors were detected.RESULTS Compared with the control group,the differences of body weight before and after treatment was much smaller in the groups of ISAP,with the smallest difference in the high-dose group of ISAP,while the capecitabine group had the greatest difference,indicating ISAP had a significant inhibiting effect on the growth of transplanted tumor in mice.The expression of RAS protein was decreased in the low-and medium-dose groups of ISAP,and the change of p-ERK was significant in the medium-and high-dose groups of ISAP.MMP2 protein expression was significantly decreased in both the low-dose and medium-dose groups of ISAP.There were no significant changes in ERK in the ISAP group compared to the capecitabine group,while RAS,MMP2,and C-MYC protein expression were reduced in the ISAP group.The expression level of C-MYC protein decreased after treated with ISAP,and the decrease was the most significant in the medium-dose group of ISAP.CONCLUSION ISAP has a potential inhibiting effect on transplanted tumor in mice,and could maintain the general conditions,physical strength and body weight of mice.The expression levels of RAS,p-ERK,MMP2 and c-myc were also decreased to a certain extent.By inhibiting the expression of upstream proteins,the expression levels of downstream proteins in ERK/MAPK signaling pathway were significantly decreased.Therefore,it can be concluded that ISAP may exert an anti-tumor effect by blocking the ERK/MAPK signaling pathway and inhibiting the expression of MMP2 and c-myc proteins. 展开更多
关键词 Colon cancer Invigorating-spleen and anticancer formula Extracellular signal-regulated kinase/mitogen-activated protein kinase signaling pathway Mice model C-MYC
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Retinoic Aacid Diminished the Expression of MMP-2 in Hyperoxia-exposed Premature Rat Lung Fibroblasts through Regulating Mitogen-activated Protein Kinases 被引量:1
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作者 李文斌 常立文 +1 位作者 容志惠 刘伟 《Journal of Huazhong University of Science and Technology(Medical Sciences)》 SCIE CAS 2011年第2期251-257,共7页
This study examined the effects of retinoic acid (RA), PD98059, SP600125 and SB203580 on the hyperoxia-induced expression and regulation of matrix metalloproteinase-2 (MMP-2) and metalloproteinase-2 (TIMP-2) in ... This study examined the effects of retinoic acid (RA), PD98059, SP600125 and SB203580 on the hyperoxia-induced expression and regulation of matrix metalloproteinase-2 (MMP-2) and metalloproteinase-2 (TIMP-2) in premature rat lung fibroblasts (LFs). LFs were exposed to hyperoxia or room air for 12 h in the presence of RA and the kinase inhibitors PD98059 (ERK1/2), SP600125 (JNK1/2) and SB203580 (p38) respectively. The expression levels of MMP-2 and TIMP-2 mRNA were detected by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR). MMP-2 activity was measured by zymography. The amount of p-ERK1/2, REK1/2, p-JNK1/2, JNK1/2, p-p38 and p38 was determined by Western blotting. The results showed that: (1) PD98059, SP600125 and SB203580 significantly inhibited p-ERK1/2, p-JNK1/2 and p-p38 respectively in LFs; (2) The expression of MMP-2 mRNA in LFs exposed to hyperoxia was decreased after treatment with RA, SP600125 and SB203580 respectively (P0.01 or 0.05), but did not change after treatment with PD98059 (P0.05). Meanwhile, RA, PD98059, SP600125 and SB203580 had no effect on the expression of TIMP-2 mRNA in LFs exposed to room air or hyperoxia (P0.05); (3) The expression of pro- and active MMP-2 experienced no change after treatment with RA or SP600125 in LFs exposed to room air (P0.05), but decreased remarkably after hyperoxia (P0.01 or 0.05). SB203580 inhibited the expression of pro- and active MMP-2 either in room air or under hyperoxia (P0.01). PD98059 exerted no effect on the expression of pro- and active MMP-2 (P0.05). It was suggested that RA had a protective effect on hyperoxia-induced lung injury by down-regulating the expression of MMP-2 through decreasing the JNK and p38 activation in hyperoxia. 展开更多
关键词 HYPEROXIA retinoic acid lung fibroblasts premature rats matrix metalloproteinase-2 mitogen-activated protein kinases
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Genome-wide identification of the mitogen-activated protein kinase kinases in pear and their functional analysis in response to black spot 被引量:1
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作者 Zan Zhang Qiming Chen +4 位作者 Luting Jia Ming Qian Qinghai Qiao Xiaosan Huang Shaoling Zhang 《Horticultural Plant Journal》 SCIE CAS CSCD 2023年第4期681-692,共12页
The mitogen-activated protein kinase(MAPK)cascade is crucial to plant growth,development,and stress responses.MAPK kinases(MAPKK)play a vital role in linking upstream MAPKK kinases(MAPKKK)with the downstream MAPK.Blac... The mitogen-activated protein kinase(MAPK)cascade is crucial to plant growth,development,and stress responses.MAPK kinases(MAPKK)play a vital role in linking upstream MAPKK kinases(MAPKKK)with the downstream MAPK.Black spot is one of the most serious fungal diseases of pear which is an important part of the fruit industry in China.The MAPKK genes have been identified in many plants,however,none has been reported in pear(Pyrus bretschneideri).In order to explore whether MAPK gene of pear is related to black spot disease,we designed this experiment.The present study investigated eight putative PbrMAPKK genes obtained from the Chinese white pear genome.The phylogenetic analysis revealed that PbrMAPKK genes were divided into A,B,C,and D groups.These PbrMAPKK genes are randomly distributed on 7 out of 17 chromosomes and mainly originated from the whole-genome duplication(WGD)event.The expression analysis of PbrMAPKK genes in seven pear tissues and the leaves of susceptible and resistant varieties after Alternaria alternata infection by quantitative real-time PCR(qRT-PCR)identified seven candidate genes associated with resistance.Furthermore,virus-induced gene silencing(VIGS)indicated that PbrMAPKK6 gene enhanced resistance to pear black spot disease in pear. 展开更多
关键词 Pyrus bretschneideri Mitogen-activated protein kinase kinase(MAPKK) Gene family Disease resistance Pear black spot
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Tale of two kinases:Protein kinase A and Ca^(2+)/calmodulin-dependent protein kinase Ⅱ in pre-diabetic cardiomyopathy 被引量:1
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作者 Pamela Gaitán-González Rommel Sánchez-Hernández +1 位作者 José-Antonio Arias-Montaño Angélica Rueda 《World Journal of Diabetes》 SCIE 2021年第10期1704-1718,共15页
Metabolic syndrome is a pre-diabetic state characterized by several biochemical and physiological alterations,including insulin resistance,visceral fat accumulation,and dyslipidemias,which increase the risk for develo... Metabolic syndrome is a pre-diabetic state characterized by several biochemical and physiological alterations,including insulin resistance,visceral fat accumulation,and dyslipidemias,which increase the risk for developing cardiovascular disease.Metabolic syndrome is associated with augmented sympathetic tone,which could account for the etiology of pre-diabetic cardiomyopathy.This review summarizes the current knowledge of the pathophysiological consequences of enhanced and sustainedβ-adrenergic response in pre-diabetes,focusing on cardiac dysfunction reported in diet-induced experimental models of pre-diabetic cardiomyopathy.The research reviewed indicates that both protein kinase A and Ca^(2+)/calmodulin-dependent protein kinase Ⅱ play important roles in functional responses mediated byβ1-adrenoceptors;therefore,alterations in the expression or function of these kinases can be deleterious.This review also outlines recent information on the role of protein kinase A and Ca^(2+)/calmodulin-dependent protein kinase Ⅱ in abnormal Ca^(2+)handling by cardiomyocytes from diet-induced models of pre-diabetic cardiomyopathy. 展开更多
关键词 Ca^(2+)/calmodulin-dependent protein kinase II protein kinase A Metabolic syndrome PRE-DIABETES Pre-diabetic cardiomyopathy β-Adrenoceptors
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Loss of monopolar spindle-binding protein 3B expression promotes colorectal cancer malignant behaviors by activation of target of rapamycin kinase/autophagy signaling
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作者 Juan Sun Jin-Xiu Zhang +8 位作者 Meng-Shi Li Meng-Bin Qin Ruo-Xi Cheng Qing-Ru Wu Qiu-Ling Chen Dan Yang Cun Liao Shi-Quan Liu Jie-An Huang 《World Journal of Gastroenterology》 SCIE CAS 2024年第26期3229-3246,共18页
BACKGROUND Monopolar spindle-binding protein 3B(MOB3B)functions as a signal transducer and altered MOB3B expression is associated with the development of human cancers.AIM To investigate the role of MOB3B in colorecta... BACKGROUND Monopolar spindle-binding protein 3B(MOB3B)functions as a signal transducer and altered MOB3B expression is associated with the development of human cancers.AIM To investigate the role of MOB3B in colorectal cancer(CRC).METHODS This study collected 102 CRC tissue samples for immunohistochemical detection of MOB3B expression for association with CRC prognosis.After overexpression and knockdown of MOB3B expression were induced in CRC cell lines,changes in cell viability,migration,invasion,and gene expression were assayed.Tumor cell autophagy was detected using transmission electron microscopy,while nude mouse xenograft experiments were performed to confirm the in-vitro results.RESULTS MOB3B expression was reduced in CRC vs normal tissues and loss of MOB3B expression was associated with poor CRC prognosis.Overexpression of MOB3B protein in vitro attenuated the cell viability as well as the migration and invasion capacities of CRC cells,whereas knockdown of MOB3B expression had the opposite effects in CRC cells.At the molecular level,microtubule-associated protein light chain 3 II/I expression was elevated,whereas the expression of matrix metalloproteinase(MMP)2,MMP9,sequestosome 1,and phosphorylated mechanistic target of rapamycin kinase(mTOR)was downregulated in MOB3B-overexpressing RKO cells.In contrast,the opposite results were observed in tumor cells with MOB3B knockdown.The nude mouse data confirmed these in-vitro findings,i.e.,MOB3B expression suppressed CRC cell xenograft growth,whereas knockdown of MOB3B expression promoted the growth of CRC cell xenografts.CONCLUSION Loss of MOB3B expression promotes CRC development and malignant behaviors,suggesting a potential tumor suppressive role of MOB3B in CRC by inhibition of mTOR/autophagy signaling. 展开更多
关键词 Colorectal cancer Monopolar spindle-binding protein 3B Mechanistic target of rapamycin kinase AUTOPHAGY Prognosis
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Tacolimus Postconditioning Alleviates Apoptotic Cell Death in Rats after Spinal Cord Ischemia-reperfusion Injury via Up-regulating Protein-Serine-Threonine Kinases Phosphorylation 被引量:2
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作者 潘峰 程艳香 +7 位作者 祝成亮 陶凤华 李章华 陶海鹰 贺斌 余铃 戢鹏 唐欢 《Journal of Huazhong University of Science and Technology(Medical Sciences)》 SCIE CAS 2013年第6期852-856,共5页
The effects of tacrolimus postconditioning on protein-serine-threonine kinases (Akt) phos- phorylation and apoptotic cell death in rats after spinal cord ischemia-reperfusion injury were investi- gated. Ninety male ... The effects of tacrolimus postconditioning on protein-serine-threonine kinases (Akt) phos- phorylation and apoptotic cell death in rats after spinal cord ischemia-reperfusion injury were investi- gated. Ninety male SD rats were randomly divided into sham operation group, ischemia-reperfusion group and tacrolimus postconditioning group. The model of spinal cord ischemia was established by means of catheterization through femoral artery and balloon dilatation. The spinal cord was reperfused 20 min after ischemia via removing saline out of balloon. The corresponding spinal cord segments were excised and determined for Akt activity in spinal cord tissue by using Western blotting at 5, 15, and 60 min after reperfusion respectively. Spinal cord tissue sections were stained immunohistochemically for detection of the phosphorylated Akt expression at 15 min after reperfusion. Flow cytometry was applied to assess apoptosis of neural cells, and dry-wet weights method was employed to measure water content in spinal cord tissue at 24 h after reperfusion. The results showed that the activities of Akt in tarcolimus postconditioning group were significantly higher than those in ischemia-reperfusion group at 5, 15, and 60 min after reperfusion (P〈0.05, P〈0.01). The Akt activities reached the peak at 15 min after reperfu- sion in ischemia-reperfusion group and tacrolimus postconditioning group. The percentage of apoptotic cells and water content in spinal cord tissue were significantly reduced (P〈0.01) in tacrolimus postcon- ditioning group as compared with those in ischemia-reperfusion group at 24 h after reperfusion. It is concluded that tacrolimus postconditioning can increase Akt activity in spinal cord tissue of rats, inhibit apoptosis of neural cells as well as tissue edema, and thereby alleviate spinal cord ischemia-reperfusion injury. 展开更多
关键词 protein-serine-threonine kinases reperfusion injury spinal cord ischemia tacrolimus post- conditioning
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Tumor suppressor protein C53 antagonizes checkpoint kinases to promote cyclin-dependent kinase 1 activation 被引量:9
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作者 Hai Jiang Jianchun Wu Chen He Wending Yang Honglin Li 《Cell Research》 SCIE CAS CSCD 2009年第4期458-468,共11页
Cyclin-dependent kinase 1 (Cdkl)/cyclin B1 complex is the driving force for mitotic entry, and its activation is tightly regulated by the G2/M checkpoint. We originally reported that a novel protein C53 (also known... Cyclin-dependent kinase 1 (Cdkl)/cyclin B1 complex is the driving force for mitotic entry, and its activation is tightly regulated by the G2/M checkpoint. We originally reported that a novel protein C53 (also known as Cdk5rap3 and LZAP) potentiates DNA damage-induced cell death by modulating the G2/M checkpoint. More recently, Wang et al. (2007) found that C53/LZAP may function as a tumor suppressor by way of inhibiting NF-kB signaling. We re- port here the identification of C53 protein as a novel regulator of Cdkl activation. We found that knockdown of C53 protein causes delayed Cdkl activation and mitotic entry. During DNA damage response, activation of checkpoint kinase 1 and 2 (Chkl and Chk2) is partially inhibited by C53 overexpression. Intriguingly, we found that C53 inter- acts with Chkl and antagonizes its function. Moreover, a portion of C53 protein is localized at the centrosome, and centrosome-targeting C53 potently promotes local Cdkl activation. Taken together, our results strongly suggest that C53 is a novel negative regulator of checkpoint response. By counteracting Chkl, C53 promotes Cdkl activation and mitotic entry in both unperturbed cell-cycle progression and DNA damage response. 展开更多
关键词 C53 Cdkl checkpoint kinases
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Clinical significance of upregulated Rho GTPase activating protein 12 causing resistance to tyrosine kinase inhibitors in hepatocellular carcinoma
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作者 Xiao-Wei Wang Yu-Xing Tang +11 位作者 Fu-Xi Li Jia-Le Wang Gao-Peng Yao Da-Tong Zeng Yu-Lu Tang Bang-Teng Chi Qin-Yan Su Lin-Qing Huang Di-Yuan Qin Gang Chen Zhen-Bo Feng Rong-Quan He 《World Journal of Gastrointestinal Oncology》 SCIE 2024年第10期4244-4263,共20页
BACKGROUND Hepatocellular carcinoma(HCC)is a major health challenge with high incidence and poor survival rates in China.Systemic therapies,particularly tyrosine kinase inhibitors(TKIs),are the first-line treatment fo... BACKGROUND Hepatocellular carcinoma(HCC)is a major health challenge with high incidence and poor survival rates in China.Systemic therapies,particularly tyrosine kinase inhibitors(TKIs),are the first-line treatment for advanced HCC,but resistance is common.The Rho GTPase family member Rho GTPase activating protein 12(ARHGAP12),which regulates cell adhesion and invasion,is a potential therapeutic target for overcoming TKI resistance in HCC.However,no studies on the expression of ARHGAP12 in HCC and its role in resistance to TKIs have been reported.AIM To unveil the expression of ARHGAP12 in HCC,its role in TKI resistance and its potential associated pathways.METHODS This study used single-cell RNA sequencing(scRNA-seq)to evaluate ARHGAP12 mRNA levels and explored its mechanisms through enrichment analysis.CellChat was used to investigate focal adhesion(FA)pathway regulation.We integrated bulk RNA data(RNA-seq and microarray),immunohistochemistry and proteomics to analyze ARHGAP12 mRNA and protein levels,correlating with clinical outcomes.We assessed ARHGAP12 expression in TKI-resistant HCC,integrated conventional HCC to explore its mechanism,identified intersecting FA pathway genes with scRNA-seq data and evaluated its response to TKI and immunotherapy.RESULTS ARHGAP12 mRNA was found to be highly expressed in malignant hepatocytes and to regulate FA.In malignant hepatocytes in high-score FA groups,MDK-[integrin alpha 6(ITGA6)+integrinβ-1(ITGB1)]showed specificity in ligand-receptor interactions.ARHGAP12 mRNA and protein were upregulated in bulk RNA,immunohistochemistry and proteomics,and higher expression was associated with a worse prognosis.ARHGAP12 was also found to be a TKI resistance gene that regulated the FA pathway.ITGB1 was identified as a crossover gene in the FA pathway in both scRNA-seq and bulk RNA.High expression of ARHGAP12 was associated with adverse reactions to sorafenib,cabozantinib and regorafenib,but not to immunotherapy.CONCLUSION ARHGAP12 expression is elevated in HCC and TKI-resistant HCC,and its regulatory role in FA may underlie the TKI-resistant phenotype. 展开更多
关键词 Hepatocellular carcinoma Focal adhesion Tyrosine kinase inhibitor Rho GTPase activating protein 12 Drug resistance Molecular mechanism BIOMARKER
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