Hydrogen sulfide (H2S) has been implicated to exhibit antioxidative properties in many models. CSE (cystathionine γ-lyase) is an important enzyme responsible for endogenous H2S production in mammalian systems, but little is known about the modulation of endogenous H2S production and its antioxidative activity. We found that inhibiting CSE activity with PAG (propargylglycine) or silencing CSE expression using an siRNA approach resulted in a greater reduction in cell viability under exposure to the oxidizing agent hydrogen peroxide (H2O2). Cellular oxidative stress also increased significantly upon PAG inhibition or CSE knockdown. Further experiments using an activity-null Y60A mutant, a hyperactive E339A mutant and a control E349A mutant demonstrated that modulation of CSE catalytic activity altered its antioxidative activity. The increased sensitivity towards H2O2-induced cytotoxicity in CSE-siRNA-transfected cells was associated with a decreased glutathione concentration (GSH) and glutathione ratio (GSH/GSSG). Incubation of cells with exogenous H2S increased the GSH concentration and GSH/GSSG ratio. Moreover, exogenous H2S preserved the cellular glutathione status under BSO (buthionine sulfoximine)-induced glutathione depletion. Taken together, the results of the present study provide molecular insights into the antioxidative activity of CSE and highlights the importance of the CSE/H2S system in maintaining cellular glutathione status.
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Research Article|
May 29 2014
The cystathionine γ-lyase/hydrogen sulfide system maintains cellular glutathione status
Zheng-Wei Lee;
Zheng-Wei Lee
*Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117599, Singapore
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Yi-Lian Low;
Yi-Lian Low
*Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117599, Singapore
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Shufen Huang;
Shufen Huang
*Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117599, Singapore
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Tianxiao Wang;
Tianxiao Wang
†Department of Pharmacy, Henan University, Kaifeng, Henan 475004, People's Republic of China
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Lih-Wen Deng
Lih-Wen Deng
1
*Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117599, Singapore
1To whom correspondence should be addressed (email bchdlw@nus.edu.sg).
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Publisher: Portland Press Ltd
Received:
October 30 2013
Revision Received:
April 02 2014
Accepted:
April 07 2014
Accepted Manuscript online:
April 07 2014
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2014 Biochemical Society
2014
Biochem J (2014) 460 (3): 425–435.
Article history
Received:
October 30 2013
Revision Received:
April 02 2014
Accepted:
April 07 2014
Accepted Manuscript online:
April 07 2014
Citation
Zheng-Wei Lee, Yi-Lian Low, Shufen Huang, Tianxiao Wang, Lih-Wen Deng; The cystathionine γ-lyase/hydrogen sulfide system maintains cellular glutathione status. Biochem J 15 June 2014; 460 (3): 425–435. doi: https://doi.org/10.1042/BJ20131434
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