胱胺抑制5-羟色胺诱导的人肺动脉平滑肌细胞增殖及机制  

Cystamine inhibits proliferation of human pulmonary arterial smooth muscle cells induced by 5-hydroxytryptamine and its mechanism

作　　者：于海英 王寒明 刘婉珠 何笛 YU Haiying;WANG Hanming;LIU Wanzhu;HE Di(Experimental Teaching Center of Basic Medicine,Jinzhou Medical University,Jinzhou,Liaoning 121001,China;Department of Pharmacology,Jinzhou Medical University,Jinzhou,Liaoning 121001,China;Department of Quality Management,Jinzhou Bentian Pharmaceutical Limited Company,Jinzhou,Liaoning 121001,China)

机构地区：[1]锦州医科大学基础医学实验教学中心,辽宁省锦州市121001 [2]锦州医科大学药理学教研室,辽宁省锦州市121001 [3]锦州本天药业有限公司质量管理部,辽宁省锦州市121001

出　　处：《中国动脉硬化杂志》2021年第4期307-311,共5页Chinese Journal of Arteriosclerosis

基　　金：辽宁省自然科学基金项目(2019-MS-139);辽宁省科技厅联合基金项目(201602316)。

摘　　要：目的研究胱胺对5-羟色胺(5-HT)诱导的人肺动脉平滑肌细胞(PASMC)增殖以及Ras同源基因家族成员A(RhoA)信号通路的影响。方法培养人PASMC,用1μmol/L 5-HT进行刺激,以胱胺进行干预。采用CCK8法观察细胞增殖情况;采用Western blot、免疫共沉淀检测RhoA信号通路各蛋白分子。结果5-HT诱导人PASMC增殖,使RhoA 5-HT化、RhoA膜转位、Rho蛋白激酶2(ROCK2)表达以及肌球蛋白磷酸酶目标亚基1(MYPT1)、蛋白激酶B(Akt)、细胞外调节蛋白激酶(ERK)磷酸化明显增加。胱胺抑制5-HT诱导的PASMC增殖、RhoA 5-HT化及MYPT1、Akt、ERK磷酸化,但对RhoA膜转位、ROCK2蛋白表达无显著影响。结论胱胺通过抑制RhoA 5-HT化从而抑制5-HT诱导的人PASMC增殖。Aim To study the effect of cystamine on the proliferation of human pulmonary arterial smooth muscle cells(PASMC)induced by 5-hydroxytryptamine(5-HT)and RhoA signaling pathway.Methods Human PASMC were cultured and stimulated with 1μmol/L 5-HT and intervened with cystamine.CCK8 assay was used to observe cell proliferation of PASMC.The protein molecules of RhoA signaling pathway were detected by Western blot and co-immunoprecipitation.Results 5-HT induced the proliferation of PASMC,and increased significantly RhoA serotonylation,RhoA membrane translocation,Rho-associated protein kinase 2(ROCK2)expression,and the phosphorylations of myosin phosphatase target subunit 1(MYPT1),protein kinase B(Akt)and extracellular regulated protein kinase(ERK).Cystamine inhibited PASMC proliferation,RhoA serotonylation and the phosphorylations of MYPT1,Akt,ERK induced by 5-HT,but had no significant effect on RhoA membrane translocation and ROCK2 protein expression.Conclusion Cystamine inhibits 5-HT-induced proliferation of human PASMC by inhibiting RhoA serotonylation.

关 键 词：5-羟色胺 肺动脉平滑肌细胞 胱胺 转谷氨酰胺酶2 

分 类 号：R96[医药卫生—药理学] R5[医药卫生—药学]