Dataset Information

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

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.

SUBMITTER: Ezerina D

PROVIDER: S-EPMC6455997 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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N-Acetyl Cysteine Functions as a Fast-Acting Antioxidant by Triggering Intracellular H<sub>2</sub>S and Sulfane Sulfur Production.

Ezeriņa Daria D Takano Yoko Y Hanaoka Kenjiro K Urano Yasuteru Y Dick Tobias P TP

Cell chemical biology 20180208 4

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 sulf ...[more]

PMID: 29429900

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Project description:Sulfane sulfur, a collective term for hydrogen polysulfide and organic persulfide, often damages cells at high concentrations. Cells can regulate intracellular sulfane sulfur levels through specific mechanisms, but these mechanisms are unclear in Corynebacterium glutamicum. OxyR is a transcription factor capable of sensing oxidative stress and is also responsive to sulfane sulfur. In this study, we found that OxyR functioned directly in regulating sulfane sulfur in C. glutamicum. OxyR binds to the promoter of katA and nrdH and regulates its expression, as revealed via in vitro electrophoretic mobility shift assay analysis, real-time quantitative PCR, and reporting systems. Overexpression of katA and nrdH reduced intracellular sulfane sulfur levels by over 30% and 20% in C. glutamicum, respectively. RNA-sequencing analysis showed that the lack of OxyR downregulated the expression of sulfur assimilation pathway genes and/or sulfur transcription factors, which may reduce the rate of sulfur assimilation. In addition, OxyR also affected the biosynthesis of L-cysteine in C. glutamicum. OxyR overexpression strain Cg-2 accumulated 183 mg/L of L-cysteine, increased by approximately 30% compared with the control (142 mg/L). In summary, OxyR not only regulated sulfane sulfur levels by controlling the expression of katA and nrdH in C. glutamicum but also facilitated the sulfur assimilation and L-cysteine synthesis pathways, providing a potential target for constructing robust cell factories of sulfur-containing amino acids and their derivatives. IMPORTANCE C. glutamicum is an important industrial microorganism used to produce various amino acids. In the production of sulfur-containing amino acids, cells inevitably accumulate a large amount of sulfane sulfur. However, few studies have focused on sulfane sulfur removal in C. glutamicum. In this study, we not only revealed the regulatory mechanism of OxyR on intracellular sulfane sulfur removal but also explored the effects of OxyR on the sulfur assimilation and L-cysteine synthesis pathways in C. glutamicum. This is the first study on the removal of sulfane sulfur in C. glutamicum. These results contribute to the understanding of sulfur regulatory mechanisms and may aid in the future optimization of C. glutamicum for biosynthesis of sulfur-containing amino acids.

Dataset Information

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

Publications

N-Acetyl Cysteine Functions as a Fast-Acting Antioxidant by Triggering Intracellular H<sub>2</sub>S and Sulfane Sulfur Production.

Similar Datasets

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Dataset Information

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

Publications

N-Acetyl Cysteine Functions as a Fast-Acting Antioxidant by Triggering Intracellular H<sub>2</sub>S and Sulfane Sulfur Production.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

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