HIF-1 Is Broadly Required for Survival in Hydrogen Sulfide.

Hydrogen sulfide is common in the environment, and is also endogenously produced by animal cells. Although hydrogen sulfide is often toxic, exposure to low levels of hydrogen sulfide improves outcomes in a variety of mammalian models of ischemia-reperfusion injury. In , the initial transcriptional response to hydrogen sulfide depends on the transcription factor, and mutant animals die when exposed to hydrogen sulfide. In this study, we use rescue experiments to identify tissues in which is required to survive exposure to hydrogen sulfide. We find that expression of from the promoter is sufficient to survive hydrogen sulfide. Although is generally considered to be a pan-neuronal promoter, we show that it is active in many nonneuronal cells as well. Using other promoters, we show that pan-neuronal expression of is not sufficient to survive exposure to hydrogen sulfide. Our data suggest that is required in many different tissues to direct the essential response to hydrogen sulfide.