The effect of certain conditions in the regulation of cystathionine γ-lyase by exogenous hydrogen sulfide in mammalian cells.

Cystathionine γ-lyase (CSE), one of three enzymes in the trans-sulfuration pathway, is responsible for the production of endogenous hydrogen sulfide (H2S) using L-cysteine or L-homocysteine as a substrate. The regulatory mechanism of CSE by exogenous H2S remains unknown. The transcription and expression of the CSE gene regulated by exogenous H2S at approximately physiologic concentrations was investigated using luciferase assay, Western blotting, and quantitative RT-PCR. The results revealed that exogenous H2S down-regulates the transcription and expression of CSE in mammalian cells at 10-80 μM. Exogenous H2S at 120 μM increases the transcription and expression of CSE significantly. At a concentration of exogenous H2S over 160 μM, the transcription and expression of CSE are inhibited completely. These findings suggest that CSE expression has not only a feedback to the enzyme itself at lower concentrations of exogenous H2S but also can be up-regulated at higher concentrations, and H2S may become toxic at higher levels.