南方医科大学学报2017，Vol.37Issue(10)：1386-1390,5.DOI:10.3969/j.issn.1673-4254.2017.10.17
亚硝基化的二硫键异构酶介导甲基苯丙胺致小鼠相关脑区α-突触核蛋白表达升高
S-nitrosylating protein disulphide isomerase mediates increased expression of α-synuclein caused by methamphetamine in mouse brain
摘要
Abstract
Objective To investigate the role of S-nitrosylation of protein disulphide isomerasec in methamphetamine(METH)-induced expression of alpha-synuclein (α-SN) in mouse hippocampus and striatum neurons. Methods Forty C57BL/6 mice were randomized equally into saline control group, METH group, L-NNA(a NOS inhibitor) group and L-NNA plus METH group.All the agents were injected intraperitoneally at an interval of 12 h,and a total of 8 injections were administered;in L-NNA plus METH group,METH was injected 30 min after L-NNA in each treatment.Western Blotting was used to detect the expression of nitric oxide synthase (NOS), α-SN, PDI and S-nitrosylation of protein disulphide isomerase (PDI-SNO) in the hippocampus and striatum of the mice,and nitric oxide(NO)levels were determined using a NO assay kit.Results In METH group, the levels of NOS, PDI-SNO, α-SN and NO all increased significantly compared with those in the control group (P<0.05).Combined treatment with L-NNA and METH,compared with METH alone,resulted in significantly lowered expression of NOS, NO, PDI-SNO and α-SN in the hippocampus and striatum of the mice (all P<0.05). No significant differences were found in NOS, NO, PDI-SNO or α-SN expressions among METH+L-NNA, L-NNA and control groups (P>0.05). Conclusion METH induces the activation of NOS and increases NO level to cause the occurrence of PDI-SNO, leading subsequently to increased expression of α-SN in mouse striatum and hippocampus.L-NNA,the inhibitor of NOS,can partly relieve nervous system toxicity induced by METH.关键词
甲基苯丙胺/二硫键异构酶/亚硝基化/α-突触核蛋白/一氧化氮合酶Key words
methamphetamine/protein disulphide isomerasec/nitrosation/α-synuclein/nitric oxide synthase引用本文复制引用
王悦,许文宁,吴小芳,朱林楠,乔红花,陈玲,刘超,邱平明..亚硝基化的二硫键异构酶介导甲基苯丙胺致小鼠相关脑区α-突触核蛋白表达升高[J].南方医科大学学报,2017,37(10):1386-1390,5.基金项目
国家自然科学基金(81373240) （81373240）
广东省自然科学基金(2014A030313300,2014A030310025) Supported by National Natural Science Foundation of China(81373240). （2014A030313300,2014A030310025）
