首页|Depression of Cav1.2 activation and expression in mast cells ameliorates allergic inflammation diseases
Depression of Cav1.2 activation and expression in mast cells ameliorates allergic inflammation diseases
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Allergic inflammation is closely related to the activation of mast cells(MCs),which is regulated by its intracellular Ca2+level,but the intake and effects of the intracellular Ca2+remain unclear.The Ca2+influx is controlled by members of Ca2+channels,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.
AllergyAsthmaMast cellCav1.2CaMKⅡ/PKC
Yongjing Zhang、Yingnan Zeng、Haoyun Bai、Wen Zhang、Zhuoyin Xue、Shiling Hu、Shemin Lu、Nan Wang
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Department of Pharmaceutical Analysis,School of Pharmacy,Xi'an Jiaotong University,Xi'an,710061,China
Key Laboratory of Environment and Genes Related to Diseases(Xi'an Jiaotong University),Ministry of Education,Xi'an,710061,China
Department of Biochemistry and Molecular Biology,School of Basic Medical Sciences,Xi'an Jiaotong University,Xi'an,710061,China
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