Sulfhydration mediates neuroprotective actions of parkin

被引：253

作者：

Vandiver, M. Scott ^{[1
]}

Paul, Bindu D. ^{[2
]}

Xu, Risheng ^{[1
]}

Karuppagounder, Senthilkumar ^{[3
,4
,5
]}

Rao, Feng ^{[2
]}

Snowman, Adele M. ^{[2
]}

Ko, Han Seok ^{[3
,4
,5
]}

Lee, Yun Il ^{[3
,4
,5
]}

Dawson, Valina L. ^{[2
,3
,4
,5
,6
]}

Dawson, Ted M. ^{[2
,3
,4
,5
]}

Sen, Nilkantha ^{[2
,7
]}

Snyder, Solomon H. ^{[1
,2
,8
]}

机构：

[1] Johns Hopkins Univ, Sch Med, Dept Pharmacol & Mol Sci, Baltimore, MD 21205 USA

[2] Johns Hopkins Univ, Sch Med, Solomon H Snyder Dept Neurosci, Baltimore, MD 21205 USA

[3] Johns Hopkins Univ, Sch Med, Inst Cell Engn, Neuroregenerat Program, Baltimore, MD 21205 USA

[4] Johns Hopkins Univ, Sch Med, Inst Cell Engn, Stem Cell Program, Baltimore, MD 21205 USA

[5] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA

[6] Johns Hopkins Univ, Sch Med, Dept Physiol, Baltimore, MD 21205 USA

[7] Med Coll Georgia, Inst Mol Med & Genet, Dept Neurol, Augusta, GA 30912 USA

[8] Johns Hopkins Univ, Sch Med, Dept Psychiat, Baltimore, MD 21205 USA

来源：

NATURE COMMUNICATIONS | 2013年 / 4卷

基金：

美国国家卫生研究院;

关键词：

HYDROGEN-SULFIDE; S-NITROSYLATION; STATISTICAL-MODEL; DOUBLE-BLIND; DISEASE; PHOSPHORYLATION; UBIQUITINATION; INSIGHTS;

D O I：

10.1038/ncomms2623

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Increases in S-nitrosylation and inactivation of the neuroprotective ubiquitin E3 ligase, parkin, in the brains of patients with Parkinson's disease are thought to be pathogenic and suggest a possible mechanism linking parkin to sporadic Parkinson's disease. Here we demonstrate that physiologic modification of parkin by hydrogen sulfide, termed sulfhydration, enhances its catalytic activity. Sulfhydration sites are identified by mass spectrometry analysis and are investigated by site-directed mutagenesis. Parkin sulfhydration is markedly depleted in the brains of patients with Parkinson's disease, suggesting that this loss may be pathologic. This implies that hydrogen sulfide donors may be therapeutic.

引用

页数：7

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