AIM: To investigate the effect of Chaiqinchengqi decoction (CQCQD) on sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) mRNA expression of pancreatic tissues in acute pancreatitis (AP) rats. METHODS: Thirty Sprague-Dawl...AIM: To investigate the effect of Chaiqinchengqi decoction (CQCQD) on sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) mRNA expression of pancreatic tissues in acute pancreatitis (AP) rats. METHODS: Thirty Sprague-Dawley (SD) rats were randomized into control group, AP group and CQCQD group (n = 3 × 10). The rats in the CQCQD group were intragastrically administered with CQCQD (10 mL/kg every 2 h) after induction of AP by intraperitoneal injection of caerulein (50 μg/kg.h × 5) within 4 h. At 6 h after the induction of AP model, pancreatic tissues were collected for the pathological observation, mRNA extraction for determination of SERCA1 and SERCA2 mRNA expression or pancreatic acinar cell isolation for measurement of fluorescence intensity (FI) of intracellular calcium ion concentration [Ca2+]i. RESULTS: There was no expression of pancreatic SERCA1 mRNA in the control group and the AP group. The expression of pancreatic SERCA2 mRNA in the AP group was down-regulated (expression ratio = 0.536; P = 0.001) compared with the control group, while that in the CQCQD group was up-regulated (expression ratio= 2.00; P = 0.012) compared with AP group. The FI of intracellular [Ca2+] of pancreatic acinar cells in the AP group (138.2 ± 23.1) was higher than the C group (111.0 ± 18.4) and the CQCQD group (118.7 ± 15.2 ) (P < 0.05) and the pancreatic pathological score in the CQCQD group was lower than that in the AP group (5.7 ± 1.9 vs 9.2 ± 2.7, P < 0.05).CONCLUSION: CQCQD can up-regulate the expression of SERCA2 mRNA of pancreatic tissues, reduce intracellular calcium overload and relieve pancreatic tissue lesions.展开更多
Background:Cytosolic Ca^(2+)plays vital roles in myogenesis and muscle development.As a major Ca^(2+)release channel of endoplasmic reticulum(ER),ryanodine receptor 1(RyR1)key mutations are main causes of severe conge...Background:Cytosolic Ca^(2+)plays vital roles in myogenesis and muscle development.As a major Ca^(2+)release channel of endoplasmic reticulum(ER),ryanodine receptor 1(RyR1)key mutations are main causes of severe congenital myopathies.The role of RyR1 in myogenic differentiation has attracted intense research interest but remains unclear.Results:In the present study,both RyR1-knockdown myoblasts and CRISPR/Cas9-based RyR1-knockout myoblasts were employed to explore the role of RyR1 in myogenic differentiation,myotube formation as well as the potential mechanism of RyR1-related myopathies.We observed that RyR1 expression was dramatically increased during the late stage of myogenic differentiation,accompanied by significantly elevated cytoplasmic Ca^(2+)concentration.Inhibition of RyR1 by siRNA-mediated knockdown or chemical inhibitor,dantrolene,significantly reduced cytosolic Ca^(2+)and blocked multinucleated myotube formation.The elevation of cytoplasmic Ca^(2+)concentration can effectively relieve myogenic differentiation stagnation by RyR1 inhibition,demonstrating that RyR1 modulates myogenic differentiation via regulation of Ca^(2+)release channel.However,RyR1-knockout-induced Ca^(2+)leakage led to the severe ER stress and excessive unfolded protein response,and drove myoblasts into apoptosis.Conclusions:Therefore,we concluded that Ca^(2+)release mediated by dramatic increase in RyR1 expression is required for the late stage of myogenic differentiation and fusion.This study contributes to a novel understanding of the role of RyR1 in myogenic differentiation and related congenital myopathies,and provides a potential target for regulation of muscle characteristics and meat quality.展开更多
Calcium ions(Ca^(2+)) are crucial intracellular second messengers in eukaryotic cells. Upon pathogen perception, plants generate a transient and rapid increase in cytoplasmic Ca^(2+)levels, which is subsequently decod...Calcium ions(Ca^(2+)) are crucial intracellular second messengers in eukaryotic cells. Upon pathogen perception, plants generate a transient and rapid increase in cytoplasmic Ca^(2+)levels, which is subsequently decoded by Ca^(2+)sensors and effectors to activate downstream immune responses. The elevation of cytosolic Ca^(2+)is commonly attributed to Ca^(2+)influx mediated by plasma membranelocalized Ca^(2+)–permeable channels. However, the contribution of Ca^(2+)release triggered by intracellular Ca^(2+)-permeable channels in shaping Ca^(2+)signaling associated with plant immunity remains poorly understood. This review discusses recent advances in understanding the mechanism underlying the shaping of Ca^(2+)signatures upon the activation of immune receptors, with particular emphasis on the identification of intracellular immune receptors as non-canonical Ca^(2+)-permeable channels. We also discuss the involvement of Ca^(2+)release from the endoplasmic reticulum in generating Ca^(2+)signaling during plant immunity.展开更多
Objective:To assess the effects of Qishen Granule(芪参颗粒, QSG) on sarcoplasmic reticulum(SR) Ca^2+ handling in heart failure(HF) model of rats and to explore the underlying molecular mechanisms. Methods:HF ...Objective:To assess the effects of Qishen Granule(芪参颗粒, QSG) on sarcoplasmic reticulum(SR) Ca^2+ handling in heart failure(HF) model of rats and to explore the underlying molecular mechanisms. Methods:HF rat models were induced by left anterior descending coronary artery ligation surgery and high-fat diet feeding. Rats were randomly divided into sham(n=10), model(n=10), QSG(n=12, 2.2 g/kg daily) and metoprolol groups(n=12, 10.5 mg/kg daily). The therapeutic effects of QSG were evaluated by echocardiography and blood lipid testing. Intracellular Ca^2+ concentration and sarco-endoplasmic reticulum ATPase 2a(SERCA2a) activity were detected by specific assay kits. Expressions of the critical regulators in SR Ca^2+ handling were evaluated by Western blot and real-time quantitative polymerase chain reaction. Results:HF model of rats developed ventricular remodeling accompanied with calcium overload and defective Ca^2+ releaseuptake cycling in cardiomyocytes. Treatment with QSG improved contractive function, attenuated ventricular remodeling and reduced the basal intracellular Ca^2+ level. QSG prevented defective Ca^2+ leak by attenuating hyperphosphorylation of ryanodine receptor 2, inhibiting expression of protein kinase A and up-regulating transcriptional expression of protein phosphatase 1. QSG also restored Ca^2+ uptake by up-regulating expression and activity of SERCA2 a and promoting phosphorylation of phospholamban. Conclusion:QSG restored SR Ca^2+cycling in HF rats and served as an ideal alternative drug for treating HF.展开更多
Piezo1 is a mechanically-gated calcium channel.Recent studies have shown that Piezo1,a mechanically-gated calcium channel,can attenuate both psychosineand lipopolysaccharide-induced demyelination.Because oligodendrocy...Piezo1 is a mechanically-gated calcium channel.Recent studies have shown that Piezo1,a mechanically-gated calcium channel,can attenuate both psychosineand lipopolysaccharide-induced demyelination.Because oligodendrocyte damage and demyelination occur in intracerebral hemorrhage,in this study,we investigated the role of Piezo1 in intracerebral hemorrhage.We established a mouse model of cerebral hemorrhage by injecting autologous blood into the right basal ganglia and found that Piezo1 was largely expressed soon(within 48 hours)after intracerebral hemorrhage,primarily in oligodendrocytes.Intraperitoneal injection of Dooku1 to inhibit Piezo1 resulted in marked alleviation of brain edema,myelin sheath loss,and degeneration in injured tissue,a substantial reduction in oligodendrocyte apoptosis,and a significant improvement in neurological function.In addition,we found that Dooku1-mediated Piezo1 suppression reduced intracellular endoplasmic reticulum stress and cell apoptosis through the PERK-ATF4-CHOP and inositol-requiring enzyme 1 signaling pathway.These findings suggest that Piezo1 is a potential therapeutic target for intracerebral hemorrhage,as its suppression reduces intracellular endoplasmic reticulum stress and cell apoptosis and protects the myelin sheath,thereby improving neuronal function after intracerebral hemorrhage.展开更多
Plants employ pattern-and effector-triggered immunity(PTI and ETI)to synergistically defend invading pathogens and insect herbivores.Both PTI and ETI can induce cytosolic Ca^(2+)spikes,despite in different spatiotempo...Plants employ pattern-and effector-triggered immunity(PTI and ETI)to synergistically defend invading pathogens and insect herbivores.Both PTI and ETI can induce cytosolic Ca^(2+)spikes,despite in different spatiotemporal patterns,to activate downstream Ca^(2+)-dependent immune signaling cascades.While multiple families of Ca^(2+)-permeable channels at the plasma membrane have been uncovered,the counterparts responsible for Ca^(2+)release from intracellular stores remain poorly understood.In a groundbreaking paper published recently by Cell,the authors reported that WeiTsing,an Arabidopsis endoplasmic reticulum(ER)-resident protein that was specifically expressed in the pericycle upon Plasmodiophora brassicae(Pb)infection,could form resistosome-like Ca^(2+)-conducting channel and protect the stele of Brassica crops from Pb colonization.As the channel activity of WeiTsing was indispensable for its immune function,the findings highlight a previously underappreciated role of Ca^(2+)release from intracellular repertoire in promoting plant disease resistance.展开更多
Pulmonary hypertension(PH) is a life-threatening disease characterized by pulmonary vascular remodeling, in which hyperproliferation of pulmonary artery smooth muscle cells(PASMCs)plays an important role. The cysteine...Pulmonary hypertension(PH) is a life-threatening disease characterized by pulmonary vascular remodeling, in which hyperproliferation of pulmonary artery smooth muscle cells(PASMCs)plays an important role. The cysteine 674(C674) in the sarcoplasmic/endoplasmic reticulum Ca^(2+)ATPase 2(SERCA2) is the critical redox regulatory cysteine to regulate SERCA2 activity. Heterozygous SERCA2 C674 S knock-in mice(SKI), where one copy of C674 was substituted by serine to represent partial C674 oxidative inactivation, developed significant pulmonary vascular remodeling resembling human PH, and their right ventricular systolic pressure modestly increased with age. In PASMCs, substitution of C674 activated inositol requiring enzyme 1 alpha(IRE1 a) and spliced X-box binding protein 1(XBP1 s) pathway, accelerated cell cycle and cell proliferation, which reversed by IRE1 a/XBP1 s pathway inhibitor 4μ8 C. In addition, suppressing the IRE1 a/XBP1 s pathway prevented pulmonary vascular remodeling caused by substitution of C674. Similar to SERCA2 a, SERCA2 b is also important to restrict the proliferation of PASMCs. Our study articulates the causal effect of C674 oxidative inactivation on the development of pulmonary vascular remodeling and PH, emphasizing the importance of C674 in restricting PASMC proliferation to maintain pulmonary vascular homeostasis. Moreover, the IRE1 a/XBP1 s pathway and SERCA2 might be potential targets for PH therapy.展开更多
Background: The calcium clearance and reactive oxygen species (ROS) generations in the coronary artery smooth muscle cells in chronic heart failure (HF) have not been fully investigated. Therefore, we attempted t...Background: The calcium clearance and reactive oxygen species (ROS) generations in the coronary artery smooth muscle cells in chronic heart failure (HF) have not been fully investigated. Therefore, we attempted to understand the gene expressions underlying the mishandling of calcium clearance and the accumulations of ROS. Methods: We initially established an animal model of chronic HF by making the left anterior descending coronary artery ligation (CAL) in rats, and then isolated the coronary artery vascular smooth muscle cells from the ischemic and the nonischemic parts of the coronary artery vessels in 12 weeks after CAL operation. The intracellular calcium concentration and ROS level were measured using flow cytometry, and the gene expressions of sarco/endoplasmic reticulum Ca2+-ATPase (SERCA2a), encoding sarcoplasmic reticulum Ca2+-ATPase 2a, encoding sodium-calcium exchanger (NCX), andp47phox encoding a subunit of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase were examined using real-time quantitative reverse transcription polymerase chain reaction and Western blotting, respectively. Results: We found that the calcium accumulation and ROS generation in the coronary artery smooth muscle cells isolated from either the ischemic or the nonischemic part of the CAL coronary artery vessel were significantly increased irrespective of blood supply (all P 〈 0.01 ). Moreover, these were accompanied by the increased expressions of NCX and p47phox, the decreased expression of S ERCA2a, and the increased amount of phosphorylated forms of p47phox in NADPH oxidase (all P 〈 0.05). Conclusions: Our results demonstrated that the disordered calcium clearance and the increased ROS generation occurred in the coronary artery smooth muscle cells in rats with chronic HF produced by ligation of the left anterior descending coronary artery (CAL), and which was found to be disassociated from blood supply, and the increased generation of ROS in the ceils was found to make concomitancy to the increased activity of NADPH oxidase in cytoplasm.展开更多
Objective: To compare the therapeutic effects of Astragaloside and Perindopril on myocardial sarco/endoplasmic reticulum Ca 2+ ATPase (SERCA) activity and the SERCA type 2 mRNA level in Coxsackievirus B 3 (CVB ...Objective: To compare the therapeutic effects of Astragaloside and Perindopril on myocardial sarco/endoplasmic reticulum Ca 2+ ATPase (SERCA) activity and the SERCA type 2 mRNA level in Coxsackievirus B 3 (CVB 3) infected cardiomyocytes. Methods: Cultured cardiomyocytes of rats were divided into normal, model, Astragaloside and Perindopril groups. The model, Astragaloside and Perindopril groups were infected with CVB 3. Meanwhile, the Astragaloside and the Perindopril groups were treated with Astragaloside (10 μg/ml) and Perindopril (1.3 μg/ml) respectively. Cytopathic effect (CPE), cardiac troponin I ( cTnI) , the SERCA activity and mRNA level of the SERCA type 2 were observed after 96 hours. Results: The CPE and cTnI of model group were significantly higher than those of normal, Astragaloside and Perindopril groups ( P <0.01). The activity and the mRNA expression of myocardial SERCA of model group were significantly lower than those of normal, Astragaloside and Perindopril groups ( P <0.01-0.05). Compared with Astragaloside group, the CPE, cTnI of Perindopril group were higher and the activity and mRNA level of Perindopril group were lower. But there were no significant difference between the two groups ( P >0.05). Conclusion: Astragaloside and Perindopril were able to reverse the down regulations of cardiac SERCA activity and mRNA expression caused by virus infection to alleviate the cardiomyocyte injury.展开更多
Calcium ions are important in many vital neuron processes, including spontaneous neurotransmitter release. Extracellular calcium has long been known to be related to spontaneous neurotransmitter release, but the detai...Calcium ions are important in many vital neuron processes, including spontaneous neurotransmitter release. Extracellular calcium has long been known to be related to spontaneous neurotransmitter release, but the detailed mechanism for the effect of intracellular Ca^2+ on synaptic release has not yet been understood. In this research, 1,2-bis-(o-aminophenoxy)-ethane-N, N, N′, N′-tetraacetic acid tetraacetoxymethyl ester (BAPTA-AM) was used to combine with cytosolic free Ca^2+ in a calcium free medium of cultured Xenopus neuromuscular junctions (NMJ), The spontaneous synaptic current (SSC) frequency was obviously reduced. Then, drugs were applied to interrupt and activate the Ca2+ release channels in the endoplasmic reticulum (ER) membrane, but the SSC frequency was not affected. The results show that spontaneous neurotransmitter release depends on intracellular rather than ER calcium in cultured Xenopus NMJ without extracellular calcium.展开更多
基金The National Natural Science Foundation of China, No. 30500684 the Medical ScienceTechnology Research Foundation of State Administration of Traditional Chinese Medicine, No. 04-05JP55
文摘AIM: To investigate the effect of Chaiqinchengqi decoction (CQCQD) on sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) mRNA expression of pancreatic tissues in acute pancreatitis (AP) rats. METHODS: Thirty Sprague-Dawley (SD) rats were randomized into control group, AP group and CQCQD group (n = 3 × 10). The rats in the CQCQD group were intragastrically administered with CQCQD (10 mL/kg every 2 h) after induction of AP by intraperitoneal injection of caerulein (50 μg/kg.h × 5) within 4 h. At 6 h after the induction of AP model, pancreatic tissues were collected for the pathological observation, mRNA extraction for determination of SERCA1 and SERCA2 mRNA expression or pancreatic acinar cell isolation for measurement of fluorescence intensity (FI) of intracellular calcium ion concentration [Ca2+]i. RESULTS: There was no expression of pancreatic SERCA1 mRNA in the control group and the AP group. The expression of pancreatic SERCA2 mRNA in the AP group was down-regulated (expression ratio = 0.536; P = 0.001) compared with the control group, while that in the CQCQD group was up-regulated (expression ratio= 2.00; P = 0.012) compared with AP group. The FI of intracellular [Ca2+] of pancreatic acinar cells in the AP group (138.2 ± 23.1) was higher than the C group (111.0 ± 18.4) and the CQCQD group (118.7 ± 15.2 ) (P < 0.05) and the pancreatic pathological score in the CQCQD group was lower than that in the AP group (5.7 ± 1.9 vs 9.2 ± 2.7, P < 0.05).CONCLUSION: CQCQD can up-regulate the expression of SERCA2 mRNA of pancreatic tissues, reduce intracellular calcium overload and relieve pancreatic tissue lesions.
基金financially supported by the National Natural Science Foundation of China (Grant No. 31790412)National key research and development program of China (Grant No. 2018YFD0500402)the National Natural Science Foundation of China (Grant No. 31672431)
文摘Background:Cytosolic Ca^(2+)plays vital roles in myogenesis and muscle development.As a major Ca^(2+)release channel of endoplasmic reticulum(ER),ryanodine receptor 1(RyR1)key mutations are main causes of severe congenital myopathies.The role of RyR1 in myogenic differentiation has attracted intense research interest but remains unclear.Results:In the present study,both RyR1-knockdown myoblasts and CRISPR/Cas9-based RyR1-knockout myoblasts were employed to explore the role of RyR1 in myogenic differentiation,myotube formation as well as the potential mechanism of RyR1-related myopathies.We observed that RyR1 expression was dramatically increased during the late stage of myogenic differentiation,accompanied by significantly elevated cytoplasmic Ca^(2+)concentration.Inhibition of RyR1 by siRNA-mediated knockdown or chemical inhibitor,dantrolene,significantly reduced cytosolic Ca^(2+)and blocked multinucleated myotube formation.The elevation of cytoplasmic Ca^(2+)concentration can effectively relieve myogenic differentiation stagnation by RyR1 inhibition,demonstrating that RyR1 modulates myogenic differentiation via regulation of Ca^(2+)release channel.However,RyR1-knockout-induced Ca^(2+)leakage led to the severe ER stress and excessive unfolded protein response,and drove myoblasts into apoptosis.Conclusions:Therefore,we concluded that Ca^(2+)release mediated by dramatic increase in RyR1 expression is required for the late stage of myogenic differentiation and fusion.This study contributes to a novel understanding of the role of RyR1 in myogenic differentiation and related congenital myopathies,and provides a potential target for regulation of muscle characteristics and meat quality.
基金supported by grants from National Natural Science Foundation of China (32370322)the National Key R&D Program of China (2022YFD1400800) to W.W.the Hainan Excellent Talent Team。
文摘Calcium ions(Ca^(2+)) are crucial intracellular second messengers in eukaryotic cells. Upon pathogen perception, plants generate a transient and rapid increase in cytoplasmic Ca^(2+)levels, which is subsequently decoded by Ca^(2+)sensors and effectors to activate downstream immune responses. The elevation of cytosolic Ca^(2+)is commonly attributed to Ca^(2+)influx mediated by plasma membranelocalized Ca^(2+)–permeable channels. However, the contribution of Ca^(2+)release triggered by intracellular Ca^(2+)-permeable channels in shaping Ca^(2+)signaling associated with plant immunity remains poorly understood. This review discusses recent advances in understanding the mechanism underlying the shaping of Ca^(2+)signatures upon the activation of immune receptors, with particular emphasis on the identification of intracellular immune receptors as non-canonical Ca^(2+)-permeable channels. We also discuss the involvement of Ca^(2+)release from the endoplasmic reticulum in generating Ca^(2+)signaling during plant immunity.
基金Supported by the National Natural Science Foundation of China(No.81530100,81470191,and 81302908)
文摘Objective:To assess the effects of Qishen Granule(芪参颗粒, QSG) on sarcoplasmic reticulum(SR) Ca^2+ handling in heart failure(HF) model of rats and to explore the underlying molecular mechanisms. Methods:HF rat models were induced by left anterior descending coronary artery ligation surgery and high-fat diet feeding. Rats were randomly divided into sham(n=10), model(n=10), QSG(n=12, 2.2 g/kg daily) and metoprolol groups(n=12, 10.5 mg/kg daily). The therapeutic effects of QSG were evaluated by echocardiography and blood lipid testing. Intracellular Ca^2+ concentration and sarco-endoplasmic reticulum ATPase 2a(SERCA2a) activity were detected by specific assay kits. Expressions of the critical regulators in SR Ca^2+ handling were evaluated by Western blot and real-time quantitative polymerase chain reaction. Results:HF model of rats developed ventricular remodeling accompanied with calcium overload and defective Ca^2+ releaseuptake cycling in cardiomyocytes. Treatment with QSG improved contractive function, attenuated ventricular remodeling and reduced the basal intracellular Ca^2+ level. QSG prevented defective Ca^2+ leak by attenuating hyperphosphorylation of ryanodine receptor 2, inhibiting expression of protein kinase A and up-regulating transcriptional expression of protein phosphatase 1. QSG also restored Ca^2+ uptake by up-regulating expression and activity of SERCA2 a and promoting phosphorylation of phospholamban. Conclusion:QSG restored SR Ca^2+cycling in HF rats and served as an ideal alternative drug for treating HF.
文摘目的探讨哮喘大鼠气道平滑肌细胞(ASMCs)中肌浆/内质网Ca^2+-ATP酶(SERCA2)的表达对IL-8分泌的影响。方法建立卵清蛋白(OVA)诱导的哮喘大鼠模型,分离原代ASMCs,分别用qRT-PCR及Western blotting、Fura PE-3/AM和ELISA法检测各组ASMCs中SERCA2表达、细胞内Ca^2+浓度([Ca^2+]i)和IL-8,利用si RNA技术下调SERCA2、毒胡萝卜素(TSG)抑制SERCA2以及吡咯烷二硫氨基甲酸(PDTC)抑制NF-κB活化,检测不同状态下IL-8的变化。结果与正常组比较,哮喘组SERCA2的表达减少,经缓激肽(BK)刺激的钙瞬变峰值明显下降,需更长时间重新摄取钙使[Ca^2+]i恢复至基线水平,IL-8基础值和经IL-17刺激后的诱导值均增加(P<0.05或0.01)。无论有无IL-17刺激,基因下调组IL-8 m RNA表达和分泌均显著增加(均P<0.01),与哮喘对照组比较差异均无统计学意义(均P>0.05)。哮喘组IκBα磷酸化和NF-κB p65核转位均较正常组增加(P<0.05或0.01),基因下调组和TSG抑制组的NF-κB p65核转位亦增加(P<0.05或0.01),而使用PDTC后,基因下调组、哮喘对照组和正常对照组在IL-17刺激诱导下的IL-8 m RNA表达和分泌均减少(P<0.05或0.01)。结论哮喘大鼠ASMCs中SERCA2表达减少,导致钙稳态的改变,可能通过增强NF-κB活化来介导IL-8分泌亢进。
基金supported by the National Natural Science Foundation of China,Nos.81901193(to HLZ)and 81901267(to YY)。
文摘Piezo1 is a mechanically-gated calcium channel.Recent studies have shown that Piezo1,a mechanically-gated calcium channel,can attenuate both psychosineand lipopolysaccharide-induced demyelination.Because oligodendrocyte damage and demyelination occur in intracerebral hemorrhage,in this study,we investigated the role of Piezo1 in intracerebral hemorrhage.We established a mouse model of cerebral hemorrhage by injecting autologous blood into the right basal ganglia and found that Piezo1 was largely expressed soon(within 48 hours)after intracerebral hemorrhage,primarily in oligodendrocytes.Intraperitoneal injection of Dooku1 to inhibit Piezo1 resulted in marked alleviation of brain edema,myelin sheath loss,and degeneration in injured tissue,a substantial reduction in oligodendrocyte apoptosis,and a significant improvement in neurological function.In addition,we found that Dooku1-mediated Piezo1 suppression reduced intracellular endoplasmic reticulum stress and cell apoptosis through the PERK-ATF4-CHOP and inositol-requiring enzyme 1 signaling pathway.These findings suggest that Piezo1 is a potential therapeutic target for intracerebral hemorrhage,as its suppression reduces intracellular endoplasmic reticulum stress and cell apoptosis and protects the myelin sheath,thereby improving neuronal function after intracerebral hemorrhage.
基金the financial support from the National Natural Science Foundation of China(32125004 and 31970278).
文摘Plants employ pattern-and effector-triggered immunity(PTI and ETI)to synergistically defend invading pathogens and insect herbivores.Both PTI and ETI can induce cytosolic Ca^(2+)spikes,despite in different spatiotemporal patterns,to activate downstream Ca^(2+)-dependent immune signaling cascades.While multiple families of Ca^(2+)-permeable channels at the plasma membrane have been uncovered,the counterparts responsible for Ca^(2+)release from intracellular stores remain poorly understood.In a groundbreaking paper published recently by Cell,the authors reported that WeiTsing,an Arabidopsis endoplasmic reticulum(ER)-resident protein that was specifically expressed in the pericycle upon Plasmodiophora brassicae(Pb)infection,could form resistosome-like Ca^(2+)-conducting channel and protect the stele of Brassica crops from Pb colonization.As the channel activity of WeiTsing was indispensable for its immune function,the findings highlight a previously underappreciated role of Ca^(2+)release from intracellular repertoire in promoting plant disease resistance.
基金supported by National Natural Science Foundation of China (31571172 and 81870343 to Xiaoyong Tong,81700237 to Pingping Hu)Chongqing Natural Science Foundation (cstc2021jcyj-msxmX 0043 to Xiaoyong Tong,China)+1 种基金Chongqing Research Program of Basic Research and Frontier Technology (cstc2016jcyjA 0407 to Xiaoyong Tong,China)Fundamental Research Funds for the Central Universities (2018CDQYYX0042 to Xiaoyong Tong,and 2018CDYXYX0027 to Pingping Hu,China)。
文摘Pulmonary hypertension(PH) is a life-threatening disease characterized by pulmonary vascular remodeling, in which hyperproliferation of pulmonary artery smooth muscle cells(PASMCs)plays an important role. The cysteine 674(C674) in the sarcoplasmic/endoplasmic reticulum Ca^(2+)ATPase 2(SERCA2) is the critical redox regulatory cysteine to regulate SERCA2 activity. Heterozygous SERCA2 C674 S knock-in mice(SKI), where one copy of C674 was substituted by serine to represent partial C674 oxidative inactivation, developed significant pulmonary vascular remodeling resembling human PH, and their right ventricular systolic pressure modestly increased with age. In PASMCs, substitution of C674 activated inositol requiring enzyme 1 alpha(IRE1 a) and spliced X-box binding protein 1(XBP1 s) pathway, accelerated cell cycle and cell proliferation, which reversed by IRE1 a/XBP1 s pathway inhibitor 4μ8 C. In addition, suppressing the IRE1 a/XBP1 s pathway prevented pulmonary vascular remodeling caused by substitution of C674. Similar to SERCA2 a, SERCA2 b is also important to restrict the proliferation of PASMCs. Our study articulates the causal effect of C674 oxidative inactivation on the development of pulmonary vascular remodeling and PH, emphasizing the importance of C674 in restricting PASMC proliferation to maintain pulmonary vascular homeostasis. Moreover, the IRE1 a/XBP1 s pathway and SERCA2 might be potential targets for PH therapy.
文摘Background: The calcium clearance and reactive oxygen species (ROS) generations in the coronary artery smooth muscle cells in chronic heart failure (HF) have not been fully investigated. Therefore, we attempted to understand the gene expressions underlying the mishandling of calcium clearance and the accumulations of ROS. Methods: We initially established an animal model of chronic HF by making the left anterior descending coronary artery ligation (CAL) in rats, and then isolated the coronary artery vascular smooth muscle cells from the ischemic and the nonischemic parts of the coronary artery vessels in 12 weeks after CAL operation. The intracellular calcium concentration and ROS level were measured using flow cytometry, and the gene expressions of sarco/endoplasmic reticulum Ca2+-ATPase (SERCA2a), encoding sarcoplasmic reticulum Ca2+-ATPase 2a, encoding sodium-calcium exchanger (NCX), andp47phox encoding a subunit of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase were examined using real-time quantitative reverse transcription polymerase chain reaction and Western blotting, respectively. Results: We found that the calcium accumulation and ROS generation in the coronary artery smooth muscle cells isolated from either the ischemic or the nonischemic part of the CAL coronary artery vessel were significantly increased irrespective of blood supply (all P 〈 0.01 ). Moreover, these were accompanied by the increased expressions of NCX and p47phox, the decreased expression of S ERCA2a, and the increased amount of phosphorylated forms of p47phox in NADPH oxidase (all P 〈 0.05). Conclusions: Our results demonstrated that the disordered calcium clearance and the increased ROS generation occurred in the coronary artery smooth muscle cells in rats with chronic HF produced by ligation of the left anterior descending coronary artery (CAL), and which was found to be disassociated from blood supply, and the increased generation of ROS in the ceils was found to make concomitancy to the increased activity of NADPH oxidase in cytoplasm.
文摘Objective: To compare the therapeutic effects of Astragaloside and Perindopril on myocardial sarco/endoplasmic reticulum Ca 2+ ATPase (SERCA) activity and the SERCA type 2 mRNA level in Coxsackievirus B 3 (CVB 3) infected cardiomyocytes. Methods: Cultured cardiomyocytes of rats were divided into normal, model, Astragaloside and Perindopril groups. The model, Astragaloside and Perindopril groups were infected with CVB 3. Meanwhile, the Astragaloside and the Perindopril groups were treated with Astragaloside (10 μg/ml) and Perindopril (1.3 μg/ml) respectively. Cytopathic effect (CPE), cardiac troponin I ( cTnI) , the SERCA activity and mRNA level of the SERCA type 2 were observed after 96 hours. Results: The CPE and cTnI of model group were significantly higher than those of normal, Astragaloside and Perindopril groups ( P <0.01). The activity and the mRNA expression of myocardial SERCA of model group were significantly lower than those of normal, Astragaloside and Perindopril groups ( P <0.01-0.05). Compared with Astragaloside group, the CPE, cTnI of Perindopril group were higher and the activity and mRNA level of Perindopril group were lower. But there were no significant difference between the two groups ( P >0.05). Conclusion: Astragaloside and Perindopril were able to reverse the down regulations of cardiac SERCA activity and mRNA expression caused by virus infection to alleviate the cardiomyocyte injury.
基金Supported by the Natural Science Foundation of Beijing (No. 5052015)
文摘Calcium ions are important in many vital neuron processes, including spontaneous neurotransmitter release. Extracellular calcium has long been known to be related to spontaneous neurotransmitter release, but the detailed mechanism for the effect of intracellular Ca^2+ on synaptic release has not yet been understood. In this research, 1,2-bis-(o-aminophenoxy)-ethane-N, N, N′, N′-tetraacetic acid tetraacetoxymethyl ester (BAPTA-AM) was used to combine with cytosolic free Ca^2+ in a calcium free medium of cultured Xenopus neuromuscular junctions (NMJ), The spontaneous synaptic current (SSC) frequency was obviously reduced. Then, drugs were applied to interrupt and activate the Ca2+ release channels in the endoplasmic reticulum (ER) membrane, but the SSC frequency was not affected. The results show that spontaneous neurotransmitter release depends on intracellular rather than ER calcium in cultured Xenopus NMJ without extracellular calcium.