Asexual propagation to increase the number of gametophytic clones via the growth of asexual haploid spores is a unique survival strategy found in marine multicellular algae. However, the mechanisms regulating the asex...Asexual propagation to increase the number of gametophytic clones via the growth of asexual haploid spores is a unique survival strategy found in marine multicellular algae. However, the mechanisms regulating the asexual life cycle are largely unknown. Here, factors involved in the regulation of production and discharge of asexual spores, so-called monospores, are identified in the marine red macroalga Porphyra yezoensis. First, enhanced discharge of monospores was found by incubation of gametophytes in ASPMT1, a modified version of the previously established synthetic medium ASP12. Comparison of the compositions of ASPMT1 and our standard medium, ESL, indicated that the Ca2+ concentration in ASPMT1 was three times lower than that in ESL medium. Thus, we modified ASPMT1 by increasing its Ca2+ concentration, resulting in reduction of monospore discharge. These findings demonstrate the role of reduced Ca2+ concentrations in enhancing monospore production and release. Moreover, it was also observed that initiation of asexual life cycle required illumination, was repressed by DCMU, and was induced by a Ca2+ ionophore in the dark. Taken together, these results indicate that photosynthesis-dependent Ca2+ influx triggers the asexual life cycle by promoting the production and discharge of monospores in P. yezoensis.展开更多
Prolife ration of neural stem cells is crucial for promoting neuronal regeneration and repairing cerebral infarction damage.Transcranial magnetic stimulation(TMS)has recently emerged as a tool for inducing endogenous ...Prolife ration of neural stem cells is crucial for promoting neuronal regeneration and repairing cerebral infarction damage.Transcranial magnetic stimulation(TMS)has recently emerged as a tool for inducing endogenous neural stem cell regeneration,but its underlying mechanisms remain unclea r In this study,we found that repetitive TMS effectively promotes the proliferation of oxygen-glucose deprived neural stem cells.Additionally,repetitive TMS reduced the volume of cerebral infa rction in a rat model of ischemic stro ke caused by middle cerebral artery occlusion,im p roved rat cognitive function,and promoted the proliferation of neural stem cells in the ischemic penumbra.RNA-sequencing found that repetitive TMS activated the Wnt signaling pathway in the ischemic penumbra of rats with cerebral ischemia.Furthermore,PCR analysis revealed that repetitive TMS promoted AKT phosphorylation,leading to an increase in mRNA levels of cell cycle-related proteins such as Cdk2 and Cdk4.This effect was also associated with activation of the glycogen synthase kinase 3β/β-catenin signaling pathway,which ultimately promotes the prolife ration of neural stem cells.Subsequently,we validated the effect of repetitive TMS on AKT phosphorylation.We found that repetitive TMS promoted Ca2+influx into neural stem cells by activating the P2 calcium channel/calmodulin pathway,thereby promoting AKT phosphorylation and activating the glycogen synthase kinase 3β/β-catenin pathway.These findings indicate that repetitive TMS can promote the proliferation of endogenous neural stem cells through a Ca2+influx-dependent phosphorylated AKT/glycogen synthase kinase 3β/β-catenin signaling pathway.This study has produced pioneering res ults on the intrinsic mechanism of repetitive TMS to promote neural function recove ry after ischemic stro ke.These results provide a stro ng scientific foundation for the clinical application of repetitive TMS.Moreover,repetitive TMS treatment may not only be an efficient and potential approach to support neurogenesis for further therapeutic applications,but also provide an effective platform for the expansion of neural stem cells.展开更多
Autoantibody against neuronal nicotinic acetylcholine receptor (nAChR) α3 subunit is implicated in severe autonomic dysfunction in the patients with autoimmune autonomic ganglionopathy (AAG). Although this autoantibo...Autoantibody against neuronal nicotinic acetylcholine receptor (nAChR) α3 subunit is implicated in severe autonomic dysfunction in the patients with autoimmune autonomic ganglionopathy (AAG). Although this autoantibody has been revealed to impair fast excitatory synaptic transmission in autonomic ganglia, its precise mechanism remains unknown. Here, we show that antibody-induced reduction of cell-surface α3 subunits result in impairment of nicotine-evoked Ca2+ influx in stably transfected human embryonic kidney cells. These effects of the antibody were remarkably inhibited by interfering with the endocytic machinery at low-temperature. We conclude that reduction of nAChR in autonomic ganglia can be mediated by the endocytosis of α3 subunits, and resulted in autonomic failure in AAG patients.展开更多
Background Abnormal insulin secretion of pancreatic beta cells is now regarded as the more primary defect than the insulin function in the etiology of type 2 diabetes.Previous studies found impaired mitochondrial func...Background Abnormal insulin secretion of pancreatic beta cells is now regarded as the more primary defect than the insulin function in the etiology of type 2 diabetes.Previous studies found impaired mitochondrial function and impaired Ca2+ influx in beta cells in diabetic patients and animal models,suggesting a role for these processes in proper insulin secretion.The aim of this study was to investigate the detailed relationship of mitochondrial function,Ca2+ influx,and defective insulin secretion.Methods We investigated mitochondrial function and morphology in pancreatic beta cell of diabetic KK-Ay mice and C57BL/6J mice.Two types of Ca2+ channel activities,L-type and store-operated Ca2+ (SOC),were evaluated using whole-cell patch-clamp recording.The glucose induced Ca2+ influx was measured by a non-invasive micro-test technique (NMT).Results Mitochondria in KK-Ay mice pancreatic beta cells were swollen with disordered cristae,and mitochondrial function decreased compared with C57BL/6J mice.Ca2+ channel activity was increased and glucose induced Ca2+ influx was impaired,but could be recovered by genipin.Conclusion Defective mitochondrial function in diabetic mice pancreatic beta cells is a key cause of abnormal insulin secretion by altering Ca2+ influx,but not via Ca2+ channel activity.展开更多
Effects of La<sup>9</sup>3+) and Gd<sup>3+</sup> on Ca<sup>2+</sup> influx were investigated in rat hepatoma H-35 cells by measuring the initial rate of<sup>45</sup>Ca&l...Effects of La<sup>9</sup>3+) and Gd<sup>3+</sup> on Ca<sup>2+</sup> influx were investigated in rat hepatoma H-35 cells by measuring the initial rate of<sup>45</sup>Ca<sup>2+</sup> uptake. It was found that the maximum initial rate of Ca<sup>2+</sup> uptake was increased six- to ten-fold at low concentrations of La<sup>3+</sup> and Gd<sup>3+</sup>. Kinetic analyses by measuring the initial rate of Ca<sup>2+</sup> influx at different external Ca<sup>2+</sup> concentrations indicated the existence of two intracellular exchangeable components in the basal Ca<sup>2+</sup> system, with low and high affinities for Ca<sup>2+</sup>,and only one class of Ca<sup>2+</sup> binding sites was observed in the La<sup>3+</sup>- or Gd<sup>3+</sup>-treated cells. For high affinity, La<sup>3+</sup> and Gd<sup>3+</sup> increased both kinetic parameters K<sub>m</sub> and V<sub>(</sub>max of basal Ca<sup>2+</sup> influx. La<sup>3+</sup> and Gd<sup>3+</sup> compete directly with Ca<sup>2+</sup> for Ca<sup>2+</sup> binding site for low affinity. The kinetics is competitive.展开更多
Here was investigated the effect of Radix Astragalus Membranaceus IAM) on Caz+ influxacross the myocardial plasma membrane and coxsackie virus B3 ( CVB3 ) -RNA replication in cultured neonatalrat heart cells infected ...Here was investigated the effect of Radix Astragalus Membranaceus IAM) on Caz+ influxacross the myocardial plasma membrane and coxsackie virus B3 ( CVB3 ) -RNA replication in cultured neonatalrat heart cells infected with CVB3 . It was found that the Oa2+ intlux could be inhibited signiticantly by AM bothin heart cells intected with CVB3 for 48 hours and in normal control heart cells. In addition. the Caz+ intluxand the amounts of CVB3-RNA in rnyocytes simultaneously intected with CVB3 and treated with AM for 48hours were statistically decreased compared with that in CVB3-infected contrOI cells. These phenomena sug-gested that AM could exert the effects of decreasing the secondary Ca2+ damages, irnproving the abnormalmyocardial electric activity and inhibiting replication of CVB3-RNA in myocardium. Thus, it is a rationalchoice to treat patients with AM in viral myocarditis.展开更多
文摘Asexual propagation to increase the number of gametophytic clones via the growth of asexual haploid spores is a unique survival strategy found in marine multicellular algae. However, the mechanisms regulating the asexual life cycle are largely unknown. Here, factors involved in the regulation of production and discharge of asexual spores, so-called monospores, are identified in the marine red macroalga Porphyra yezoensis. First, enhanced discharge of monospores was found by incubation of gametophytes in ASPMT1, a modified version of the previously established synthetic medium ASP12. Comparison of the compositions of ASPMT1 and our standard medium, ESL, indicated that the Ca2+ concentration in ASPMT1 was three times lower than that in ESL medium. Thus, we modified ASPMT1 by increasing its Ca2+ concentration, resulting in reduction of monospore discharge. These findings demonstrate the role of reduced Ca2+ concentrations in enhancing monospore production and release. Moreover, it was also observed that initiation of asexual life cycle required illumination, was repressed by DCMU, and was induced by a Ca2+ ionophore in the dark. Taken together, these results indicate that photosynthesis-dependent Ca2+ influx triggers the asexual life cycle by promoting the production and discharge of monospores in P. yezoensis.
基金supported by the National Natural Science Foundation of China,Nos.81672261(to XH),81972151(to HZ),82372568(to JL)the Natural Science Foundation of Guangdong Province,Nos.2019A1515011106(to HZ),2023A1515030080(to JL)。
文摘Prolife ration of neural stem cells is crucial for promoting neuronal regeneration and repairing cerebral infarction damage.Transcranial magnetic stimulation(TMS)has recently emerged as a tool for inducing endogenous neural stem cell regeneration,but its underlying mechanisms remain unclea r In this study,we found that repetitive TMS effectively promotes the proliferation of oxygen-glucose deprived neural stem cells.Additionally,repetitive TMS reduced the volume of cerebral infa rction in a rat model of ischemic stro ke caused by middle cerebral artery occlusion,im p roved rat cognitive function,and promoted the proliferation of neural stem cells in the ischemic penumbra.RNA-sequencing found that repetitive TMS activated the Wnt signaling pathway in the ischemic penumbra of rats with cerebral ischemia.Furthermore,PCR analysis revealed that repetitive TMS promoted AKT phosphorylation,leading to an increase in mRNA levels of cell cycle-related proteins such as Cdk2 and Cdk4.This effect was also associated with activation of the glycogen synthase kinase 3β/β-catenin signaling pathway,which ultimately promotes the prolife ration of neural stem cells.Subsequently,we validated the effect of repetitive TMS on AKT phosphorylation.We found that repetitive TMS promoted Ca2+influx into neural stem cells by activating the P2 calcium channel/calmodulin pathway,thereby promoting AKT phosphorylation and activating the glycogen synthase kinase 3β/β-catenin pathway.These findings indicate that repetitive TMS can promote the proliferation of endogenous neural stem cells through a Ca2+influx-dependent phosphorylated AKT/glycogen synthase kinase 3β/β-catenin signaling pathway.This study has produced pioneering res ults on the intrinsic mechanism of repetitive TMS to promote neural function recove ry after ischemic stro ke.These results provide a stro ng scientific foundation for the clinical application of repetitive TMS.Moreover,repetitive TMS treatment may not only be an efficient and potential approach to support neurogenesis for further therapeutic applications,but also provide an effective platform for the expansion of neural stem cells.
文摘Autoantibody against neuronal nicotinic acetylcholine receptor (nAChR) α3 subunit is implicated in severe autonomic dysfunction in the patients with autoimmune autonomic ganglionopathy (AAG). Although this autoantibody has been revealed to impair fast excitatory synaptic transmission in autonomic ganglia, its precise mechanism remains unknown. Here, we show that antibody-induced reduction of cell-surface α3 subunits result in impairment of nicotine-evoked Ca2+ influx in stably transfected human embryonic kidney cells. These effects of the antibody were remarkably inhibited by interfering with the endocytic machinery at low-temperature. We conclude that reduction of nAChR in autonomic ganglia can be mediated by the endocytosis of α3 subunits, and resulted in autonomic failure in AAG patients.
基金This study was supported by grants from Fund of Capital Medical Development and Research (No. 2009-1020) and Tsinghua-Yue-Yuen Medical Science Foundation (No.20240000531 and No.20240000568)
文摘Background Abnormal insulin secretion of pancreatic beta cells is now regarded as the more primary defect than the insulin function in the etiology of type 2 diabetes.Previous studies found impaired mitochondrial function and impaired Ca2+ influx in beta cells in diabetic patients and animal models,suggesting a role for these processes in proper insulin secretion.The aim of this study was to investigate the detailed relationship of mitochondrial function,Ca2+ influx,and defective insulin secretion.Methods We investigated mitochondrial function and morphology in pancreatic beta cell of diabetic KK-Ay mice and C57BL/6J mice.Two types of Ca2+ channel activities,L-type and store-operated Ca2+ (SOC),were evaluated using whole-cell patch-clamp recording.The glucose induced Ca2+ influx was measured by a non-invasive micro-test technique (NMT).Results Mitochondria in KK-Ay mice pancreatic beta cells were swollen with disordered cristae,and mitochondrial function decreased compared with C57BL/6J mice.Ca2+ channel activity was increased and glucose induced Ca2+ influx was impaired,but could be recovered by genipin.Conclusion Defective mitochondrial function in diabetic mice pancreatic beta cells is a key cause of abnormal insulin secretion by altering Ca2+ influx,but not via Ca2+ channel activity.
文摘Effects of La<sup>9</sup>3+) and Gd<sup>3+</sup> on Ca<sup>2+</sup> influx were investigated in rat hepatoma H-35 cells by measuring the initial rate of<sup>45</sup>Ca<sup>2+</sup> uptake. It was found that the maximum initial rate of Ca<sup>2+</sup> uptake was increased six- to ten-fold at low concentrations of La<sup>3+</sup> and Gd<sup>3+</sup>. Kinetic analyses by measuring the initial rate of Ca<sup>2+</sup> influx at different external Ca<sup>2+</sup> concentrations indicated the existence of two intracellular exchangeable components in the basal Ca<sup>2+</sup> system, with low and high affinities for Ca<sup>2+</sup>,and only one class of Ca<sup>2+</sup> binding sites was observed in the La<sup>3+</sup>- or Gd<sup>3+</sup>-treated cells. For high affinity, La<sup>3+</sup> and Gd<sup>3+</sup> increased both kinetic parameters K<sub>m</sub> and V<sub>(</sub>max of basal Ca<sup>2+</sup> influx. La<sup>3+</sup> and Gd<sup>3+</sup> compete directly with Ca<sup>2+</sup> for Ca<sup>2+</sup> binding site for low affinity. The kinetics is competitive.
文摘Here was investigated the effect of Radix Astragalus Membranaceus IAM) on Caz+ influxacross the myocardial plasma membrane and coxsackie virus B3 ( CVB3 ) -RNA replication in cultured neonatalrat heart cells infected with CVB3 . It was found that the Oa2+ intlux could be inhibited signiticantly by AM bothin heart cells intected with CVB3 for 48 hours and in normal control heart cells. In addition. the Caz+ intluxand the amounts of CVB3-RNA in rnyocytes simultaneously intected with CVB3 and treated with AM for 48hours were statistically decreased compared with that in CVB3-infected contrOI cells. These phenomena sug-gested that AM could exert the effects of decreasing the secondary Ca2+ damages, irnproving the abnormalmyocardial electric activity and inhibiting replication of CVB3-RNA in myocardium. Thus, it is a rationalchoice to treat patients with AM in viral myocarditis.