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In this study, we aimed to investigate the role of nitrosative stress and S\u2010nitrosylation of protein disulfide isomerase (PDI) in the formation of SOD1 aggregates. Our data show that with disease progression inducible nitric oxide synthase (iNOS) was up\u2010regulated, which generated high levels of nitric oxide (NO) and subsequently induced S\u2010nitrosylation of PDI in the spinal cord of mutant SOD1 transgenic mice. This was further confirmed by <jats:italic>in vitro<\/jats:italic> observation that treating SH\u2010SY5Y cells with NO donor S\u2010nitrosocysteine triggered a dose\u2010dependent formation of S\u2010nitrosylated PDI. When mutant SOD1 was over\u2010expressed in SH\u2010SY5Y cells, the iNOS expression was up\u2010regulated, and NO generation was consequently increased. Furthermore, both S\u2010nitrosylation of PDI and the formation of mutant SOD1 aggregates were detected in the cells expressing mutant SOD1<jats:sup>G93A<\/jats:sup>. Blocking NO generation with the NOS inhibitor N\u2010nitro\u2010<jats:sc>l<\/jats:sc>\u2010arginine attenuated the S\u2010nitrosylation of PDI and inhibited the formation of mutant SOD1 aggregates. We conclude that NO\u2010mediated S\u2010nitrosylation of PDI is a contributing factor to the accumulation of mutant SOD1 aggregates in amyotrophic lateral sclerosis.<\/jats:p>","DOI":"10.1111\/jnc.12046","type":"journal-article","created":{"date-parts":[[2012,10,8]],"date-time":"2012-10-08T13:23:53Z","timestamp":1349702633000},"page":"45-58","source":"Crossref","is-referenced-by-count":45,"title":["S\u2010nitrosylated protein disulfide isomerase contributes to mutant SOD1 aggregates in amyotrophic lateral sclerosis"],"prefix":"10.1111","volume":"124","author":[{"given":"Xueping","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Human Anatomy and Cell Science University of Manitoba Winnipeg Manitoba Canada"},{"name":"Department of Neurology, West China Hospital Sichuan University Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaosha","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Human Anatomy and 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