S-nitrosylating protein disulphide isomerase mediates increased expression of α-synuclein caused by methamphetamine in mouse brain
WANG Yue
XU Wenning
WU Xiaofang
ZHU Linnan
QIAO Honghua
CHEN Ling
LIU Chao
QIU Pingming
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.
Keywords：methamphetamineprotein disulphide isomerasecnitrosationα-synucleinnitric oxide synthase
Publication Date：2017-01-01
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：5( 1386-1390 )