Cystathionine-{gamma}-lyase/hydrogen sulfide system maintains cellular glutathione status

Hydrogen sulfide (H2S) has been implicated to exhibit an antioxidative property in many models. Cystathionine-γ-lyase (CSE) 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 propargylglycine (PAG) or silencing CSE expression by siRNA approach resulted in greater reduction of cell viability under exposure to oxidizing agent, hydrogen peroxide (H2O2). Cellular oxidative stress also increased significantly upon PAG inhibition or CSE knockdown. Further experiments using activity-null Y60A mutant, hyperactivity E339A mutant and 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 decreased reduced glutathione concentration (GSH) and glutathione ratio (GSH/GSSG). Incubation of the cells with exogenous H2S also increased GSH concentration and GSH/GSSG ratio. Moreover, exogenous H2S preserved the cellular glutathione status under buthionine sulfoximine (BSO)-induced glutathione depletion. Taken together, this study provides molecular insights into the antioxidative activity of CSE and highlights the importance of CSE/H2S system in maintaining cellular glutathione status.
Source: BJ Energy - Category: Biochemistry Authors: Tags: BJ Energy Source Type: research