Format

Send to

Choose Destination
Cell Chem Biol. 2018 Apr 19;25(4):447-459.e4. doi: 10.1016/j.chembiol.2018.01.011. Epub 2018 Feb 8.

N-Acetyl Cysteine Functions as a Fast-Acting Antioxidant by Triggering Intracellular H2S and Sulfane Sulfur Production.

Author information

1
Division of Redox Regulation, DKFZ-ZMBH Alliance, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany; Faculty of Biosciences, Heidelberg University, 69120 Heidelberg, Germany.
2
Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
3
Division of Redox Regulation, DKFZ-ZMBH Alliance, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany. Electronic address: t.dick@dkfz.de.

Abstract

The cysteine prodrug N-acetyl cysteine (NAC) is widely used as a pharmacological antioxidant and cytoprotectant. It has been reported to lower endogenous oxidant levels and to protect cells against a wide range of pro-oxidative insults. As NAC itself is a poor scavenger of oxidants, the molecular mechanisms behind the antioxidative effects of NAC have remained uncertain. Here we show that NAC-derived cysteine is desulfurated to generate hydrogen sulfide, which in turn is oxidized to sulfane sulfur species, predominantly within mitochondria. We provide evidence suggesting the possibility that sulfane sulfur species produced by 3-mercaptopyruvate sulfurtransferase and sulfide:quinone oxidoreductase are the actual mediators of the immediate antioxidative and cytoprotective effects provided by NAC.

KEYWORDS:

N-acetyl cysteine; antioxidant; cysteine; cytoprotection; hydrogen sulfide; hydropersulfides; roGFP2; stress resistance; sulfane sulfur; sulfide:quinone oxidoreductase

PMID:
29429900
PMCID:
PMC6455997
DOI:
10.1016/j.chembiol.2018.01.011
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center