Allergic inflammation is closely related to the activation of mast cells(MCs),which is regulated by its intracellular Ca^(2+) plevel,but the intake and effects of the intracellular Ca^(2+) premain unclear.The Ca^(2+) ...Allergic inflammation is closely related to the activation of mast cells(MCs),which is regulated by its intracellular Ca^(2+) plevel,but the intake and effects of the intracellular Ca^(2+) premain unclear.The Ca^(2+) pinflux is controlled by members of Ca^(2+) pchannels,among which calcium voltage-gated channel subunit alpha1 C(CaV1.2)is the most robust.This study aimed to reveal the role and underlying mechanism of MC CaV1.2 in allergic inflammation.We found that CaV1.2 participated in MC activation and allergic inflammation.Nimodipine(Nim),as a strong CaV1.2-specific antagonist,ameliorated allergic inflammation in mice.Further,CaV1.2 activation in MC was triggered by phosphatizing at its Ser1928 through protein kinase C(PKC),which calcium/calmodulin-dependent protein kinase II(CaMKII)catalyzed.Overexpression or knockdown of MC CaV1.2 influenced MC activation.Importantly,CaV1.2 expression in MC had detrimental effects,while its deficiency ameliorated allergic pulmonary inflammation.Results provide novel insights into CaV1.2 function and a potential drug target for controlling allergic inflammation.展开更多
目的研究犬肺静脉肌袖(PVs)CaV1.2和ERG的mRNA水平,初步探讨其表达与PVs独特离子流特点的关系。方法8只健康犬左上PVs和左房游离壁心肌组织,用逆转录聚合酶链反应法分析CaV1.2和ERG的mRNA在不同部位的表达差别。结果PVs内CaV1.2的mRNA...目的研究犬肺静脉肌袖(PVs)CaV1.2和ERG的mRNA水平,初步探讨其表达与PVs独特离子流特点的关系。方法8只健康犬左上PVs和左房游离壁心肌组织,用逆转录聚合酶链反应法分析CaV1.2和ERG的mRNA在不同部位的表达差别。结果PVs内CaV1.2的mRNA水平较左房降低(1.16±0.07 vs 1.32±0.05,P<0.05),而ERG的mRNA水平较左房有显著的升高(0.87±0.08 vs 0.55±0.09,P<0.05)。结论PVs心肌细胞和左房心肌细胞的CaV1.2和ERG的mRNA表达有差异,此可能导致其离子流特点的不同。展开更多
基金funded by National Natural Science Foundation of China(Grant Nos.:81930096 and 82274063).
文摘Allergic inflammation is closely related to the activation of mast cells(MCs),which is regulated by its intracellular Ca^(2+) plevel,but the intake and effects of the intracellular Ca^(2+) premain unclear.The Ca^(2+) pinflux is controlled by members of Ca^(2+) pchannels,among which calcium voltage-gated channel subunit alpha1 C(CaV1.2)is the most robust.This study aimed to reveal the role and underlying mechanism of MC CaV1.2 in allergic inflammation.We found that CaV1.2 participated in MC activation and allergic inflammation.Nimodipine(Nim),as a strong CaV1.2-specific antagonist,ameliorated allergic inflammation in mice.Further,CaV1.2 activation in MC was triggered by phosphatizing at its Ser1928 through protein kinase C(PKC),which calcium/calmodulin-dependent protein kinase II(CaMKII)catalyzed.Overexpression or knockdown of MC CaV1.2 influenced MC activation.Importantly,CaV1.2 expression in MC had detrimental effects,while its deficiency ameliorated allergic pulmonary inflammation.Results provide novel insights into CaV1.2 function and a potential drug target for controlling allergic inflammation.
文摘目的研究犬肺静脉肌袖(PVs)CaV1.2和ERG的mRNA水平,初步探讨其表达与PVs独特离子流特点的关系。方法8只健康犬左上PVs和左房游离壁心肌组织,用逆转录聚合酶链反应法分析CaV1.2和ERG的mRNA在不同部位的表达差别。结果PVs内CaV1.2的mRNA水平较左房降低(1.16±0.07 vs 1.32±0.05,P<0.05),而ERG的mRNA水平较左房有显著的升高(0.87±0.08 vs 0.55±0.09,P<0.05)。结论PVs心肌细胞和左房心肌细胞的CaV1.2和ERG的mRNA表达有差异,此可能导致其离子流特点的不同。
