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Promotion of structural plasticity in area V2 of visual cortex prevents against object recognition memory deficits in aging and Alzheimer's disease rodents
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作者 Irene Navarro-Lobato Mariam Masmudi-Martín +8 位作者 Manuel F.López-Aranda Juan F.López-Téllez Gloria Delgado Pablo Granados-Durán Celia Gaona-Romero Marta Carretero-Rey Sinforiano Posadas María E.Quiros-Ortega Zafar U.Khan 《Neural Regeneration Research》 SCIE CAS CSCD 2024年第8期1835-1841,共7页
Memory deficit,which is often associated with aging and many psychiatric,neurological,and neurodegenerative diseases,has been a challenging issue for treatment.Up till now,all potential drug candidates have failed to ... Memory deficit,which is often associated with aging and many psychiatric,neurological,and neurodegenerative diseases,has been a challenging issue for treatment.Up till now,all potential drug candidates have failed to produce satisfa ctory effects.Therefore,in the search for a solution,we found that a treatment with the gene corresponding to the RGS14414protein in visual area V2,a brain area connected with brain circuits of the ventral stream and the medial temporal lobe,which is crucial for object recognition memory(ORM),can induce enhancement of ORM.In this study,we demonstrated that the same treatment with RGS14414in visual area V2,which is relatively unaffected in neurodegenerative diseases such as Alzheimer s disease,produced longlasting enhancement of ORM in young animals and prevent ORM deficits in rodent models of aging and Alzheimer’s disease.Furthermore,we found that the prevention of memory deficits was mediated through the upregulation of neuronal arbo rization and spine density,as well as an increase in brain-derived neurotrophic factor(BDNF).A knockdown of BDNF gene in RGS14414-treated aging rats and Alzheimer s disease model mice caused complete loss in the upregulation of neuronal structural plasticity and in the prevention of ORM deficits.These findings suggest that BDNF-mediated neuronal structural plasticity in area V2 is crucial in the prevention of memory deficits in RGS14414-treated rodent models of aging and Alzheimer’s disease.Therefore,our findings of RGS14414gene-mediated activation of neuronal circuits in visual area V2 have therapeutic relevance in the treatment of memory deficits. 展开更多
关键词 behavioral performance brain-derived neurotrophic factor cognitive dysfunction episodic memory memory circuit activation memory deficits memory enhancement object recognition memory prevention of memory loss regulator of g protein signaling
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Regulator of G protein signaling 6 mediates exercise-induced recovery of hippocampal neurogenesis,learning,and memory in a mouse model of Alzheimer’s disease
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作者 Mackenzie M.Spicer Jianqi Yang +5 位作者 Daniel Fu Alison N.DeVore Marisol Lauffer Nilufer S.Atasoy Deniz Atasoy Rory A.Fisher 《Neural Regeneration Research》 SCIE CAS 2025年第10期2969-2981,共13页
Hippocampal neuronal loss causes cognitive dysfunction in Alzheimer’s disease.Adult hippocampal neurogenesis is reduced in patients with Alzheimer’s disease.Exercise stimulates adult hippocampal neurogenesis in rode... Hippocampal neuronal loss causes cognitive dysfunction in Alzheimer’s disease.Adult hippocampal neurogenesis is reduced in patients with Alzheimer’s disease.Exercise stimulates adult hippocampal neurogenesis in rodents and improves memory and slows cognitive decline in patients with Alzheimer’s disease.However,the molecular pathways for exercise-induced adult hippocampal neurogenesis and improved cognition in Alzheimer’s disease are poorly understood.Recently,regulator of G protein signaling 6(RGS6)was identified as the mediator of voluntary running-induced adult hippocampal neurogenesis in mice.Here,we generated novel RGS6fl/fl;APP_(SWE) mice and used retroviral approaches to examine the impact of RGS6 deletion from dentate gyrus neuronal progenitor cells on voluntary running-induced adult hippocampal neurogenesis and cognition in an amyloid-based Alzheimer’s disease mouse model.We found that voluntary running in APP_(SWE) mice restored their hippocampal cognitive impairments to that of control mice.This cognitive rescue was abolished by RGS6 deletion in dentate gyrus neuronal progenitor cells,which also abolished running-mediated increases in adult hippocampal neurogenesis.Adult hippocampal neurogenesis was reduced in sedentary APP_(SWE) mice versus control mice,with basal adult hippocampal neurogenesis reduced by RGS6 deletion in dentate gyrus neural precursor cells.RGS6 was expressed in neurons within the dentate gyrus of patients with Alzheimer’s disease with significant loss of these RGS6-expressing neurons.Thus,RGS6 mediated voluntary running-induced rescue of impaired cognition and adult hippocampal neurogenesis in APP_(SWE) mice,identifying RGS6 in dentate gyrus neural precursor cells as a possible therapeutic target in Alzheimer’s disease. 展开更多
关键词 adult hippocampal neurogenesis Alzheimer’s disease dentate gyrus EXERCISE learning/memory neural precursor cells regulator of g protein signaling 6(RgS6)
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Targeting the nitric oxide/cGMP signaling pathway to treat chronic pain 被引量:5
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作者 Dan-Yang Li Shao-Jie Gao +6 位作者 Jia Sun Long-Qing Zhang Jia-Yi Wu Fan-He Song Dai-Qiang Liu Ya-Qun Zhou Wei Mei 《Neural Regeneration Research》 SCIE CAS CSCD 2023年第5期996-1003,共8页
Nitric oxide(NO)/cyclic guanosine 3′,5′-monophosphate(cGMP) signaling has been shown to act as a mediator involved in pain transmission and processing. In this review, we summarize and discuss the mechanisms of the ... Nitric oxide(NO)/cyclic guanosine 3′,5′-monophosphate(cGMP) signaling has been shown to act as a mediator involved in pain transmission and processing. In this review, we summarize and discuss the mechanisms of the NO/cGMP signaling pathway involved in chronic pain, including neuropathic pain, bone cancer pain, inflammatory pain, and morphine tolerance. The main process in the NO/cGMP signaling pathway in cells involves NO activating soluble guanylate cyclase, which leads to subsequent production of cGMP. cGMP then activates cGMP-dependent protein kinase(PKG), resulting in the activation of multiple targets such as the opening of ATP-sensitive K+ channels. The activation of NO/cGMP signaling in the spinal cord evidently induces upregulation of downstream molecules, as well as reactive astrogliosis and microglial polarization which participate in the process of chronic pain. In dorsal root ganglion neurons, natriuretic peptide binds to particulate guanylyl cyclase, generating and further activating the cGMP/PKG pathway, and it also contributes to the development of chronic pain. Upregulation of multiple receptors is involved in activation of the NO/cGMP signaling pathway in various pain models. Notably the NO/cGMP signaling pathway induces expression of downstream effectors, exerting both algesic and analgesic effects in neuropathic pain and inflammatory pain. These findings suggest that activation of NO/cGMP signaling plays a constituent role in the development of chronic pain, and this signaling pathway with dual effects is an interesting and promising target for chronic pain therapy. 展开更多
关键词 bone cancer pain chronic pain cyclic gMP dorsal root ganglion inflammatory pain morphine tolerance neuropathic pain nitric oxide protein kinase g spinal cord
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Long non-coding RNA CDKN2B-AS1 promotes hepatocellular carcinoma progression via E2F transcription factor 1/G protein subunit alpha Z axis
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作者 Zhi-Gang Tao Yu-Xiao Yuan Guo-Wei Wang 《World Journal of Gastrointestinal Oncology》 SCIE 2023年第11期1974-1987,共14页
BACKGROUND A series of long non-coding RNAs(lncRNAs)have been reported to play a crucial role in cancer biology.Some previous studies report that lncRNA CDKN2B-AS1 is involved in some human malignancies.However,its ro... BACKGROUND A series of long non-coding RNAs(lncRNAs)have been reported to play a crucial role in cancer biology.Some previous studies report that lncRNA CDKN2B-AS1 is involved in some human malignancies.However,its role in hepatocellular carcinoma(HCC)has not been fully deciphered.AIM To decipher the role of CDKN2B-AS1 in the progression of HCC.METHODS CDKN2B-AS1 expression in HCC was detected by quantitative real-time polymerase chain reaction.The malignant phenotypes of Li-7 and SNU-182 cells were detected by the CCK-8 method,EdU method,and flow cytometry,respectively.RNA immunoprecipitation was executed to confirm the interaction between CDKN2B-AS1 and E2F transcription factor 1(E2F1).Luciferase reporter assay and chromatin immunoprecipitation were performed to verify the binding of E2F1 to the promoter of G protein subunit alpha Z(GNAZ).E2F1 and GNAZ were detected by western blot in HCC cells.RESULTS In HCC tissues,CDKN2B-AS1 was upregulated.Depletion of CDKN2B-AS1 inhibited the proliferation of HCC cells,and the depletion of CDKN2B-AS1 also induced cell cycle arrest and apoptosis.CDKN2B-AS1 could interact with E2F1.Depletion of CDKN2B-AS1 inhibited the binding of E2F1 to the GNAZ promoter region.Overexpression of E2F1 reversed the biological effects of depletion of CDKN2B-AS1 on the malignant behaviors of HCC cells.CONCLUSION CDKN2B-AS1 recruits E2F1 to facilitate GNAZ transcription to promote HCC progression. 展开更多
关键词 Hepatocellular carcinoma CDKN2B-AS1 E2F transcription factor 1 g protein subunit alpha Z Proliferation
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Melanocortin 4 receptor mutation in obesity
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作者 Gumpeny R Sridhar Lakshmi Gumpeny 《World Journal of Experimental Medicine》 2024年第4期120-128,共9页
Obesity is increasingly prevalent worldwide,with genetic factors contributing to its development.The hypothalamic leptin-melanocortin pathway is central to the regulation of appetite and weight;leptin activates the pr... Obesity is increasingly prevalent worldwide,with genetic factors contributing to its development.The hypothalamic leptin-melanocortin pathway is central to the regulation of appetite and weight;leptin activates the proopiomelanocortin neurons,leading to the production of melanocortin peptides;these in turn act on melanocortin 4 receptors(MC4R)which suppress appetite and increase energy expenditure.MC4R mutations are responsible for syndromic and non-syndromic obesity.These mutations are classified based on their impact on the receptor's life cycle:i.e.null mutations,intracellular retention,binding defects,signaling defects,and variants of unknown function.Clinical manifestations of MC4R mutations include early-onset obesity,hyperphagia,and metabolic abnormalities such as hyperinsulinemia and dyslipidemia.Management strategies for obesity due to MC4R mutations have evolved with the development of targeted therapies such as Setmelanotide,an MC4R agonist which can reduce weight and manage symptoms without adverse cardiovascular effects.Future research directions must include expansion of population studies to better understand the epidemiology of MC4R mutations,exploration of the molecular mechanisms underlying MC4R signaling,and development of new therapeutic agents.Understanding the interaction between MC4R and other genetic and environmental factors will be key to advancing both the prevention and treatment of obesity. 展开更多
关键词 Leptin-melanocortin pathway DOWNSTREAM g protein Cyclic AMP MUTATION Obesity syndromes Screening Setmelanotide
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反相高效液相色谱法测定牛初乳保健食品中免疫球蛋白G的含量 被引量:1
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作者 罗娇依 刘彤彤 +3 位作者 曹进 赵溪 孙姗姗 张旭光 《中国食物与营养》 2022年第9期20-26,共7页
目的:建立一种测定牛初乳保健食品中免疫球蛋白G的反相高效液相色谱法。方法:样品采用磷酸盐缓冲液涡旋振荡提取,经Protein G固相免疫亲和小柱净化后,使用高效液相色谱仪(搭载紫外检测器)检测,紫外波长为280 nm,采用C反相色谱柱(4.6... 目的:建立一种测定牛初乳保健食品中免疫球蛋白G的反相高效液相色谱法。方法:样品采用磷酸盐缓冲液涡旋振荡提取,经Protein G固相免疫亲和小柱净化后,使用高效液相色谱仪(搭载紫外检测器)检测,紫外波长为280 nm,采用C反相色谱柱(4.6×250 mm, 5μm)分析。流动相为0.1%三氟乙酸-水溶液和乙腈,梯度洗脱分离,外标法定量。结果:色谱分离过程可在10 min内完成,免疫球蛋白G在10~100μg/mL范围内线性良好,相关系数R=0.999 6。检出限为0.5 g/kg,定量限为1.7 g/kg。3个浓度水平的方法加标回收率为92.2~97.5%,方法精密度为0.20~1.18%。样品经前处理后4℃冰箱内保存,在24 h内稳定性良好。结论:该方法特异性强,灵敏度、精确度高,符合方法学验证要求,可快速、准确地对保健食品中免疫球蛋白G进行分析检测。 展开更多
关键词 免疫球蛋白g 保健食品 高效液相色谱法 Protein g免疫亲和柱
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Heterotrimeric G protein α subunit is involved in rice brassinosteroid response 被引量:31
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作者 Lei Wang Yun-Yuan Xu +3 位作者 Qi-Bin Ma Dan Li Zhi-Hong Xu Kang Chong 《Cell Research》 SCIE CAS CSCD 2006年第12期916-922,共7页
Heterotrimeric G proteins are known to function as messengers in numerous signal transduction pathways.The nullmutation of RGA(rice heterotrimeric G protein α subunit),which encodes the α subunit of heterotrimeric G... Heterotrimeric G proteins are known to function as messengers in numerous signal transduction pathways.The nullmutation of RGA(rice heterotrimeric G protein α subunit),which encodes the α subunit of heterotrimeric G proteinin rice,causes severe dwarfism and reduced responsiveness to gibberellic acid in rice.However,less is known aboutheterotrimeric G protein in brassinosteroid(BR)signaling,one of the well-understood phytohormone pathways.In thepresent study,we used root elongation inhibition assay,lamina inclination assay and coleoptile elongation analysis todemonstrated reduced sensitivity of dl mutant plants(caused by the null mutation of RGA)to 24-epibrassinolide(24-epiBL),which belongs to brassinosteroids and plays a wide variety of roles in plant growth and development.Moreover,RGA transcript level was decreased in 24-epiBL-treated seedlings in a dose-dependent manner.Our results show thatRGA is involved in rice brassinosteroid response,which may be beneficial to elucidate the molecular mechanisms of Gprotein signaling and provide a novel perspective to understand BR signaling in higher plants. 展开更多
关键词 heterotrimeric g protein α subunit dl mutant BR signaling RICE
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Heterotrimeric G-protein is involved in phytochrome A-mediated cell death of Arabidopsis hypocotyls 被引量:4
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作者 Qing Wei Wenbin Zhou Guangzhen Hu Jiamian Wei Hongquan Yang Jirong Huang 《Cell Research》 SCIE CAS CSCD 2008年第9期949-960,共12页
The heterotrimeric guanine nucleotide-binding protein (G-protein) has been demonstrated to mediate various signaling pathways in plants. However, its role in phytochrome A (phyA) signaling remains elusive. In this... The heterotrimeric guanine nucleotide-binding protein (G-protein) has been demonstrated to mediate various signaling pathways in plants. However, its role in phytochrome A (phyA) signaling remains elusive. In this study, we discover a new phyA-mediated phenotype designated far-red irradiation (FR) preconditioned cell death, which occurs only in the hypocotyls of FR-grown seedlings following exposure to white light (WL). The cell death is mitigated in the Gα mutant gpal but aggravated in the Gβ mutant agbl in comparison with the wild type (WT), indicative of antagonistic roles of GPA1 and AGBI in the phyA-mediated cell-death pathway. Further investigation indicates that FR-induced accumulation of nonphotoconvertible protochlorophyllide (Pchlide^633), which generates reactive oxygen species (ROS) on exposure to WL, is required for FR-preconditioned cell death. Moreover, ROS is mainly detected in chloroplasts using the fluorescent probe. Interestingly, the application of H2O2 to dark-grown seedlings results in a phenotype similar to FR-preconditioned cell death. This reveals that ROS is a critical mediator for the ceil death. In addition, we observe that agb1 is more sensitive to H2O2 than WT seedlings, indicating that the G-protein may also modify the sensitivity of the seedlings to ROS stress. Taking these results together, we infer that the G-protein may be involved in the phyA signaling pathway to regulate FR-preconditioned cell death ofArabidopsis hypocotyls. A possible mechanism underlying the involvement of the G-protein in phyA signaling is discussed in this study. 展开更多
关键词 heterotrimeric g protein phytochrome A ROS cell death Pchlide
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G-protein beta 3 subunit polymorphisms and essential hypertension: a case-control association study in northern Han Chinese 被引量:4
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作者 Mei LI Bei ZHANG Chuang LI Jie-Lin LIU Li-Juan WANG Ya LIU Zuo-Guang WANG Shao-Jun WEN 《Journal of Geriatric Cardiology》 SCIE CAS CSCD 2015年第2期127-134,共8页
Objective To explore the association between the three polymorphisms [ C825T, C1429T and G(-350)A] of the gene encoding the G protein beta 3 subunit (GNB3) and hypertension by performing a case-control study in th... Objective To explore the association between the three polymorphisms [ C825T, C1429T and G(-350)A] of the gene encoding the G protein beta 3 subunit (GNB3) and hypertension by performing a case-control study in the northern Han Chinese population. Methods We recnaited 731 hypertensive patients and 673 control subjects (the calculated power value was 〉 0.8). Genotyping was performed to identify C825T, C1429T and G(-350)A polymorphisms using the TaqMan assay. Comparisons of allelic and genotypic frequencies between cases and controls were made by using the chi-square test. Logistic regression analyses were performed to investigate the relationships between the three polymorphisms of GNB3 gene under different genetic models (additive, dominant and recessive models). Results The genotype dis- tribution and allele frequencies of C825T, C1429T and G(-350)A polymorphisms did not differ significantly between hypertensive patients and control subjects, either when the full sample was assessed, or when the sample was stratified by gender. No significant association was observed between C825T, C 1429T and G(-350)A polymorphisms and the risk of essential hypertension in any genetic model. Linkage dis- equilibrium was only detected between C825T and C 1429T polymorphisms. Haplotype analyses observed that none of the three estimated haplotypes significantly increased the risk of hypertension. Conclusions Our study suggested that the GNB3 gene polymorphisms [C825T, C 1429T and G(-350)A] were not significantly associated with essential hypertension in northern Han Chinese population. 展开更多
关键词 g protein beta 3 subunit gene HAPLOTYPE Hypertension POLYMORPHISM
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Association of the GNAS1 T393C polymorphism with tumor stage and survival in gastric cancer 被引量:3
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作者 Hakan Alakus Stefan P Mnig +10 位作者 Ute Warnecke-Eberz Gül Alakus Günther Winde Uta Drebber Klaus J Schmitz Kurt W Schmid Kathrin Riemann Winfried Siffert Elfriede Bollschweiler Arnulf H Hlscher Ralf Metzger 《World Journal of Gastroenterology》 SCIE CAS CSCD 2009年第48期6061-6067,共7页
AIM: To analyze the impact of the GNAS1 T393C polymorphism on prognosis and histopathology of gastric cancer. METHODS: Genomic DNA was extracted from paraffinembedded tissues of 122 patients with primary gastric car... AIM: To analyze the impact of the GNAS1 T393C polymorphism on prognosis and histopathology of gastric cancer. METHODS: Genomic DNA was extracted from paraffinembedded tissues of 122 patients with primary gastric carcinoma and from the blood of 820 healthy white individuals. Allelic discrimination was performed by quantitative real-time polymerase chain reaction. Genotyping was correlated with histopathologic parameters and with overall survival according to the Kaplan-Meier approach and with multivariate analysis by multiple stepwise regression. RESULTS: Thirty-nine (32%) patients displayed a CC genotype, 57 (46.7%) a CT genotype and 26 (21.3%) a TT genotype. The frequency of the C allele (fC) in the patient group was 0.55, which was not significantly different from that of healthy blood donors. The distribution was compatible with the Hardy-Weinberg equilibrium. Analysis of clinicopathological parameters did not show any significant correlation of the T393C genotype with gender (P = 0.50), differentiation (P = 0.29), pT-category (P = 0.19), pN-category (P = 0.30), pM-category (P = 0.25), R-category (P = 0.95), the classifications according to WHO (P = 0.34), Lauren (P = 0.16), Goseki (P = 1.00) and Ming (P =0.74). Dichotomization between C+ (CC+CT) and C-genotypes (FI), however, revealed significantly more advanced tumor stages (P = 0.023) and lower survival rates (P = 0.043) for C allele carriers. CONCLUSION: The present study provides strong evidence to suggest that the GNAS1 T393C allele carrier status influences tumor progression and survival in gastric cancer with higher tumor stages and a worse outcome for C allele carriers. 展开更多
关键词 gastric cancer g Protein POLYMORPHISM PROgNOSIS Tumor stage
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Gene Cloning and Expression Analysis of G Protein αq Subunit from Helicoverpa assulta (Guenée) 被引量:3
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作者 QIAO Qi LI Hai-chao YUAN Guo-hui GUO Xian-ru LUO Mei-hao 《Agricultural Sciences in China》 CAS CSCD 2008年第2期187-192,共6页
The cDNA encoding the G protein αq subunit was isolated from the antennae of Helicoverpa assulta (Guen6e) by reverse transcription polymerase chain reaction (RT-PCR) and named as HassGαq. Sequencing analysis sho... The cDNA encoding the G protein αq subunit was isolated from the antennae of Helicoverpa assulta (Guen6e) by reverse transcription polymerase chain reaction (RT-PCR) and named as HassGαq. Sequencing analysis showed that the fulllength of HassGαq open reading frame (ORF) is 1 062 bp, 353 amino acid residues are encoded. The predicted molecular weights (MW) and isoelectric point (PI) are 41.5 kD and 5.15, respectively. HassGαq gene was then constructed into expression vector pGEX-4T-2 for over expression in prokaryotic cells. The SDS-PAGE and Western blot analysis showed that induced by Isopropyl-β-D-Thiogalactoside (IPTG), the GST-HassGαq fusion protein is expressed in Escherichia coil BL21, and its MW was found to be about 66 kD nearly equal to the predicted. In addition, RT-PCR analysis showed that the expressions of HassGαq are not tissue specific. 展开更多
关键词 Helicoverpa assulta g protein α subunit gene cloning prokaryotic expression expression pattern
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Characterization of reference genes for qPCR analysis in various tissues of the Fujian oyster Crassostrea angulata 被引量:2
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作者 濮菲 杨丙晔 柯才焕 《Chinese Journal of Oceanology and Limnology》 SCIE CAS CSCD 2015年第4期838-845,共8页
Accurate quantification of transcripts using quantitative real-time polymerase chain reaction (qPCR) depends on the identification of reliable reference genes for normalization. This study aimed to identify and vali... Accurate quantification of transcripts using quantitative real-time polymerase chain reaction (qPCR) depends on the identification of reliable reference genes for normalization. This study aimed to identify and validate seven reference genes, including actin-2 (ACT-2), elongation factor 1 alpha (EF-1α), elongation factor 1 beta (EF-1β), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), ubiquitin (UBQ), β-tubulin (β-TUB), and 18 S ribosomal RNA, from Crassostrea angulata, a valuable marine bivalve cultured worldwide. Transcript levels of the candidate reference genes were examined using qPCR analysis and showed differential expression patterns in the mantle, gill, adductor muscle, labial palp, visceral mass, hemolymph and gonad tissues. Quantitative data were analyzed using the geNorm software to assess the expression stability of the candidate reference genes, revealing that β-TUB and UBQ were the most stable genes. The commonly used GAPDH and 18S rRNA showed low stability, making them unsuitable candidates in this system. The expression pattern of the G protein β-subunit gene (Gβ) across tissue types was also examined and normalized to the expression of each or both of UBQ andβ-TUB as internal controls. This revealed consistent trends with all three normalization approaches, thus validating the reliability of UBQ and β-TUB as optimal internal controls. The study provides the first validated reference genes for accurate data normalization in transcript profiling in Crassostrea angulata, which will be indispensable for further fimetional genomics studies in this economically valuable marine bivalve. 展开更多
关键词 Crassostrea angulata gene expression quantitative real-time PCR internal control gene g protein β-subunit gene
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Acupuncture at the San Jiao meridian affects brain stem tissue G protein content in a rat migraine model 被引量:1
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作者 Sue Wang Wei Li Guangwei Zhong Zhenyan Li Lingbo Wen 《Neural Regeneration Research》 SCIE CAS CSCD 2008年第9期958-961,共4页
BACKGROUND: G protein is closely associated with vasomotion. Vasomotor dysfunction accompanies migraine attack. OBJECTIVE: To investigate the effects of the San Jiao meridian acupuncture on G protein content in a ra... BACKGROUND: G protein is closely associated with vasomotion. Vasomotor dysfunction accompanies migraine attack. OBJECTIVE: To investigate the effects of the San Jiao meridian acupuncture on G protein content in a rat migraine model. DESIGN, TIME AND SETTING: The present randomized grouping, cellular and molecular biological level trial was performed at the Institute of Integrated Traditional Chinese and Western Medicine, Xiangya Hospital, Central South University & Key Laboratory for Tumor Proteomics of Ministry of Health between October 2003 and June 2004. MATERIALS: Forty healthy, male, Sprague Dawtey rats were included in this study. The G6805-2A electro-acupuncture apparatus was a product of Shanghai Huayi Medical Instrument Factory, China. Nitroglycerin was produced by Guangzhou Mingxing Pharmaceutical Factory, China. Antibodies against inhibitory and stimulatory G proteins were purchased from Sigma Chemical Company, USA. METHODS: All 40 rats were randomly and evenly divided into 4 groups. In the blank control group, the rats remained untouched. Rats from the normal control group were subcutaneously administered 2 mL/kg physiological saline. In the model group, migraine was induced with a subcutaneous injection of 10 mg/kg nitroglycerin (5 g/L), and the rats received no further treatment. In the acupuncture-treated group, 30 minutes after migraine induction, acupuncture was performed at the bilateral Waiguan (SJ 5) and Yifeng (SJ 17) points, with an acupuncture depth of 1 mm. Electric-stimulation parameters of 20 Hz for low frequency, 40 Hz for high frequency, and 0.5-1.0 mA for current intensity were set. Ten acupuncture sessions were applied, with 20-minute low-frequency and 20-minute high-frequency stimulation and 3 seconds of interval time. MAIN OUTCOME MEASURES: Inhibitory and stimulatory G protein contents were detected by Western blot analysis. RESULTS: At 4 hours after migraine induction, compared with the blank control and normal control groups stimulatory G protein concentration was significantly increased, while inhibitory G protein levels were significantly decreased in the model group (P 〈 0.01 ). In the acupuncture-treated group, both stimulatory and inhibitory G protein concentrations were significantly increased following acupuncture treatment (P 〈 0.01), but stimulatory G protein levels were less and the inhibitory G protein concentrations were greater compared to the model group (P 〈 0.01 ). There was no significant difference in stimulatory and inhibitory G protein levels between the blank control and normal control groups (P 〉 0.05). CONCLUSION: Dysfunctional G protein signal transductions in the rat brain stem may be responsible tor migraine attack. Acupuncture at the San Jiao meridian ameliorates migraines by mediating the G protein signal transduction pathway. 展开更多
关键词 ACUPUNCTURE g protein: migraine San Jiao meridian Western blot
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Study of signal transduction factors involved in mycoparasitic response of Trichoderma atroviride 被引量:1
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作者 Scala V Zeilinger S +7 位作者 Ambrosino P Brunner K Reithner B Mach R L Woo S L Cristilli M Scala F Lorito M 《浙江大学学报(农业与生命科学版)》 CAS CSCD 北大核心 2004年第4期451-451,共1页
Numerous Trichoderma spp. are mycoparasites and commercially applied as biological control agents against a large number of plant pathogenic fungi. The mycoparasitic interaction is host-specific and several research s... Numerous Trichoderma spp. are mycoparasites and commercially applied as biological control agents against a large number of plant pathogenic fungi. The mycoparasitic interaction is host-specific and several research strategies have been applied to identify the main genes and compounds involved in the antagonist-plant-pathogen three-way interaction. During mycoparasitism, signals from the host fungus are recognised by Trichoderma, stimulating antifungal activities that are accompanied by morphological changes and the secretion of hydrolytic enzymes and antibiotics. Interestingly some morphological changes appeared highly conserved in the strategy of pathogenicity within the fungal world, i.e. the formation of appressoria as well as the secretion of hydrolytic enzymes seem to be general mechanisms of attack both for plant pathogens and mycoparasitic antagonists. This knowledge is being used to identify receptors and key components of signalling pathways involved in fungus-fungus interaction. For this purpose we have cloned the first genes (tmk1, tga1, tga3) from T. atroviride showing a high similarity to MAP kinase and G protein subunits (see abstract by Zeilinger et al.), which have been found to have an important role in pathogenicity by Magnaporthe grisea. To identify the function and involvement of these factors in mycoparasitism by T. atroviride, tmk1, tga1, tga3 disruptant strains were produced. The knock-out mutants were tested by in vivo biocontrol assays for their ability to inhibit soil and foliar plant pathogens such as Rhizoctonia solani, Pythium ultimum and Botrytis cinerea . Disruption of these genes corresponded to a complete loss of biocontrol ability, suggesting a significant role in mycoparasitism. In particular, it has been suggested that tga3 regulates the expression of chitinase-encoding genes, the secretion of the corresponding enzymes and the process of conidiation. Comparative proteome analysis of wild type and disruptants supported this hypothesis, and indicated many changes in the protein profiles of T. atroviride in different interaction conditions with plants and pathogenic hosts. 展开更多
关键词 PATHOgENICITY MAP kinase g proteins
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Gene Cloning and Tissue-Specific Expression of G Protein β Subunit in Microplitis mediator (Hymenoptera: Braconidae) 被引量:1
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作者 ZHANG Shuai ZHANG Yong-jun +2 位作者 CUI Jin-jie GAO Xi-wu GUO Yu-yuan 《Agricultural Sciences in China》 CAS CSCD 2010年第4期568-576,共9页
A gene encoding a novel G protein β subunit of β1 subclass, GβMmed was isolated from Microplitis mediator (Hymenoptera: Braconidae). The full-length sequence of GβMmed is 1 119 bp, the cDNA contains a 1 023 bp... A gene encoding a novel G protein β subunit of β1 subclass, GβMmed was isolated from Microplitis mediator (Hymenoptera: Braconidae). The full-length sequence of GβMmed is 1 119 bp, the cDNA contains a 1 023 bp open reading frame that encodes a protein with 340 amino acids, and the predicted molecular weight of GβMmed is 37.23 kDa and isoelectric point is 5.86. By the quantitative real-time RT-PCR method, the tissue-specific expression and quantitative changes in the developmental expression profile of GβMmed were detected. It was found that GβMmed was abundantly expressed in M. mediator antennae, head (without antennae), thorax, abdomen, legs and the wings, and especially at high levels in abdomen. In antennae, expression varied through 1st day before emergence to 5-d-old adults, and had equal expression levels detected in females and males in total. In head, GβMmed expresses while initially high in females, and have another peaked in stage 4 and 1st day, in males showed a peak of GβMmed expression prior to emergence and relatively low levels after emergence. In female abdomen GβMmed expression levels have two peaks in stage 1 and the 5th d, but just have one peak in male abdomen in stage 1. In all other tissues expression was low and stable. 展开更多
关键词 Microplitis mediator g protein β subunit quantitative real-time RT-PCR expression pattern
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Dendroaspis natriuretic peptide relaxes gastric antral circular smooth muscle of guinea-pig through thecGMP/cGMP-dependent protein kinase pathway 被引量:1
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作者 Chun-Yu Cai Zheng-Xu Cai +5 位作者 Xin-Yi Gu Lu-Juan Shan Yong-Xiao Wang Xue-Zhe Yin Qing-Hui Qi Hui-Shu Guo 《World Journal of Gastroenterology》 SCIE CAS CSCD 2008年第35期5461-5466,共6页
AIM: To systematically investigate if cGMP/cGMP- dependent protein kinase G (PKG) signaling pathway may participate in dendroaspis natriuretic peptide (DNP)-induced relaxation of gastric circular smooth muscle. METHOD... AIM: To systematically investigate if cGMP/cGMP- dependent protein kinase G (PKG) signaling pathway may participate in dendroaspis natriuretic peptide (DNP)-induced relaxation of gastric circular smooth muscle. METHODS: The content of cGMP in guinea pig gastric antral smooth muscle tissue and perfusion solution were measured using radioimmunoassay; spontaneous contraction of gastric antral circular muscles recorded using a 4-channel physiograph; and Ca2+-activated K+ currents (IK(Ca)) and spontaneous transient outward currents (STOCs) in isolated gastric antral myocytes were recorded using the whole-cell patch clamp technique. RESULTS: DNP markedly enhanced cGMP levels in gastric antral smooth muscle tissue and in the perfusion medium. DNP induced relaxation in gastricantral circular smooth muscle, which was inhibited by KT5823, a cGMP-dependent PKG inhibitor. DNP increased IK(Ca). This effect was almost completely blocked by KT5823, and partially blocked by LY83583, an inhibitor of guanylate cyclase to change the production of cGMP. DNP also increased STOCs. The effect of DNP on STOCs was abolished in the presence of KT5823, but not affected by KT-5720, a PKA-specific inhibitor. CONCLUSION: DNP activates IK(Ca) and relaxes guinea-pig gastric antral circular smooth muscle via the cGMP/PKG-dependent singling axis instead of cAMP/ PKA pathway. 展开更多
关键词 Dendroaspis natriuretic peptide Cyclic guanosine monophosphate Protein kinase g Proteinkinase A gastric motility
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Glabridin Relaxes Vascular Smooth Muscles by Activating BK_(Ca) Channels and Inhibiting Phosphodiesterase in Human Saphenous Vein 被引量:2
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作者 Cengiz Giüven Ali Parlar 《Current Medical Science》 SCIE CAS 2021年第2期381-389,共9页
The aim of the current study was to investigate the pharmacological activity of glabridinon the isolated human saphenous vein (SV) and explore the underlying mechanisms. Samples of patients' SVs were removed durin... The aim of the current study was to investigate the pharmacological activity of glabridinon the isolated human saphenous vein (SV) and explore the underlying mechanisms. Samples of patients' SVs were removed during bypass surgery, and 4-mm lengths of the vessels were placedin Krebs solution at ±4℃ and hung in an isolated organ bath to assess their contraction/relaxationresponses. The contraction/relaxation responses were recorded to observe if the cyclic guanosinemonophosphate (cGMP)/protein kinase G (PKG) pathway mediates the relaxant effect of glabridinafter treatment with blockers like ODQ (a guanylate cyclase inhibitor), KT5823 (a PKG inhibitor),isobutylmethylxanthine [IBMX, a phosphodiesterase (PDE) inhibitor], and cantharidin [Cant,a myosin light-chain phosphatase (MLCP) inhibitor]. Moreover, nitric oxide (NO), cGMP, andPKG levels in SV tissues were determined by ELISA after incubation with glabridin, N(o)-nitro-L-arginine methyl ester (L-Name, a NO synthetase inhibitor), phenylephrine (PE), ODQ, IBMX,and KT5823. The results showed that glabridin relaxed the vascular smooth muscle of humanSV pretreated with PE in a dose-dependent manner, which was independent of the endothelium.The vasorelaxant effect of glabridin was only inhibited by iberiotoxin (IbTX), Cant, and KT5823.Glabridin increased cGMP and PKG levels in SV homogenates, whereas it did not alter the NOlevel. The enhancing efects of cGMP and PKG levels by glabridin were abolished by ODQ andKT5823. In conclusion, glabridin has a vasorelaxant effect, which is associated with the activationof BKc. channels and inhibition of PDE. 展开更多
关键词 gLABRIDIN BKCa channels human saphenous vein(SV)grafts cyclic guanosine monophosphate(cgMP) protein kinase g(PKg)
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Occurrence of cGMP/nitric oxide-sensitive store-operated calcium entry in fibroblasts and its effect on matrix metalloproteinase secretion 被引量:1
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作者 Yong Huang Min-Qiang Lu Hua Li Chi Xu Shu-Hong Yi Gui-Hua Chen 《World Journal of Gastroenterology》 SCIE CAS CSCD 2006年第34期5483-5489,共7页
AIM: To examine the existence of Nitric oxide/ cGMP sensitive store-operated Ca^2+ entry in mouse fibroblast NIH/3T3 cells and its influence on matrix metalloproteinase (MMP) production and adhesion ability of fib... AIM: To examine the existence of Nitric oxide/ cGMP sensitive store-operated Ca^2+ entry in mouse fibroblast NIH/3T3 cells and its influence on matrix metalloproteinase (MMP) production and adhesion ability of fibroblasts. METHODS: NIH/3T3 cells were cultured. Confocal laser scanning microscopy was used to examine the existence of thapsigargin-induced store-operated Ca^2+ entry in fibroblasts. Gelatin zymography and semiquantitative reverse transcriptase-polymerase chain reaction (RTPCR) were employed to detect the involvement of [Ca^2+]i and NO/cGMP in MMP secretion. The involvement of NO/ cGMP-sensitive Ca^2+ entry in adhesion was determined using matrigel-coated culture plates. RESULTS: 8-bromo-cGMP inhibited the thapsigargin-induced Ca^2+ entry in 3T3 cells. The cGMP-induced inhibition was abolished by an inhibitor of protein kinase G, KT5823 (1μmol/L). A similar effect on the Ca^2+ entry was observed in 3T3 cells in response to a NO donor, (±)-S-nitroso-N-acetylpenicillamine (SNAP). The inhibitory effect of SNAP on the thapsigargin-induced Ca^2+ entry was also observed, indicating NO/cGMP-regulated Ca^2+ entry in 3T3 cells. Results of gelatin zymography assay showed that addition of extracellular Ca^2+ concentration induced MMP release and activation in a dose-dependent manner. RT-PCR also showed that cGMP and SNAP reduced the production of MMP mRNA in 3T3 cells. Experiments investigating adhesion potentials demonstrated that cGMP and SNAP could upgrade 3T3 cell attachment rate to the matrigel-coated culture plates.CONCLUSION: NO/cGMP sensitive store-operated Ca^2+ entry occurs in fibroblasts, and attenuates their adhesion potentials through its influence on MMP secretion. 展开更多
关键词 CgMP Nitric oxide Protein kinase g Storeoperated Ca^2+ entry Matrix metalloproteinase FIBROBLAST
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G protein signalling involved in host recognition and mycoparasitism-related chitinase expression in Trichoderma atroviride
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作者 Susanne Zeilinger Barbara Reithner +4 位作者 Kurt Brunner Valeria Scala Isabel Peiβl Matteo Lorito Robert L Mach 《浙江大学学报(农业与生命科学版)》 CAS CSCD 北大核心 2004年第4期448-448,共1页
Mycoparasitic species of Trichoderma are commercially applied as biological control agents against various fungal pathogens. The mycoparasitic interaction is host specific and includes recognition, attack and subseque... Mycoparasitic species of Trichoderma are commercially applied as biological control agents against various fungal pathogens. The mycoparasitic interaction is host specific and includes recognition, attack and subsequent penetration and killing of the host. Investigations on the underlying events revealed that Trichoderma responds to multiple signals from the host (e.g. lectins or other ligands such as low molecular weight components released from the host’s cell wall) and host attack is accompanied by morphological changes and the secretion of hydrolytic enzymes and antibiotics. Degradation of the cell wall of the host fungus is-besides glucanases and proteases-mainly achieved by chitinases. In vivo studies showed that the ech42 gene (encoding endochitinase 42) is expressed before physical contact of Trichoderma with its host, probably representing one of the earliest events in mycoparasitism, whereas Nag1 (N-acetylglucosaminidase) plays a key role in the general induction of the chitinolytic enzyme system of T. atroviride . Investigations on the responsible signal transduction pathways of T. atroviride led to the isolation of several genes encoding key components of the cAMP and MAP kinase signaling pathways, as alpha and β subunits of heterotrimeric G proteins, the regulatory subunit of cAMP-dependent protein kinase, adenylate cyclase, and three MAP kinases. Analysis of knockout mutants, generated by Agrobacterium-mediated transformation, revealed that at least two alpha-subunits of heterotrimeric G proteins are participating in mycoparasitism-related signal transduction. The Tga1 G alpha subunit was shown to be involved in mycoparasitism-related processes such as chitinase expression and overproduction of toxic secondary metabolites, whereas Tga3 was found to be completely avirulent showing defects in chitinase formation and host recognition. 展开更多
关键词 TRICHODERMA g proteins signal transduction BIOCONTROL host recognition.
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Signal transduction of bombesin-induced circular smooth muscle cell contraction in cat esophagus
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作者 Sung-Uk Park Chang-Yell Shin +6 位作者 Jung-Su Ryu Hyen-O La Sun-Young Park Hyun-Ju Song Young-Sil Min Dong-Seok Kim Uy-Dong Sohn 《World Journal of Gastroenterology》 SCIE CAS CSCD 2006年第14期2259-2263,共5页
AIM: To investigate the mechanism of bombesin-induced circular smooth muscle cell contraction in cat esophagus. METHODS: Specific G protein or phospholipase C involved in cat esophagus contraction was identified, mu... AIM: To investigate the mechanism of bombesin-induced circular smooth muscle cell contraction in cat esophagus. METHODS: Specific G protein or phospholipase C involved in cat esophagus contraction was identified, muscle cells were permeabilized with saponin. After per- meabilization of muscle cells, the Gi3 antibody inhibited bombesin-induced smooth muscle cell contraction. RESULTS: Incubation of permeabilized circular muscle cells with PLC-β3 antibody could inhibit bombesin-induced contraction. H-7, chelerythrine (PKC inhibitor) and genistein (protein tyrosine kinase inhibitor) inhibited bombesin-induced contraction, but DAG kinase inhibitor, R59949, could not inhibit it. To examine which mitogen-activated protein kinase (MAPK) was involved in bombesin-induced contTaction, the specific MAPK inhibitors (MEK inhibitor, PD98059 and p38 MAPK inhibitor, SB202190) were used. Preincubation of PD98059 blocked the contraction induced by bombesin in a concentration-dependent manner. However, SB202190 had no effects on contraction. CONCLUSION: Bombesin-induced circular muscle cell contraction in cat esophagus is mediated via a PKC or a PTK-dependent pathway or p44/p42 HAPK pathway. 展开更多
关键词 BOMBESIN g protein Phospholipase C Protein kinase C Protein tyrosine kinase MAP Kinase Cell contraction
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