Abstract
Hydrogen sulfide (H2S) has dramatic physiological effects on animals that are associated with improved survival. C. elegans grown in H2S are long-lived and thermotolerant. To identify mechanisms by which adaptation to H2S effects physiological functions, we have measured transcriptional responses to H2S exposure. Using microarray analysis we observe rapid changes in the abundance of specific mRNAs. The number and magnitude of transcriptional changes increased with the duration of H2S exposure. Functional annotation suggests that genes associated with protein homeostasis are upregulated upon prolonged exposure to H2S. Previous work has shown that the hypoxia-inducible transcription factor, HIF-1, is required for survival in H2S. In fact, we show that hif-1 is required for most, if not all, early transcriptional changes in H2S. Moreover, our data demonstrate that SKN-1, the C. elegans homologue of NRF2, also contributes to H2S-dependent changes in transcription. We show that these results are functionally important, as skn-1 is essential to survive exposure to H2S. Our results suggest a model in which HIF-1 and SKN-1 coordinate a broad transcriptional response to H2S that culminates in a global reorganization of protein homeostasis networks.
Highlights
Exogenous H2S has dramatic effects on mammalian physiology that can improve survival in changing environmental conditions
The hif-1 transcription factor is required to survive exposure to H2S [8]. hif1 is a highly conserved bHLH transcription factor that is wellknown for its role in coordinating the transcriptional response to hypoxia in all animals, including C. elegans [9,10]
To investigate the transcriptional responses to H2S in C. elegans, we employed a microarray approach to identify mRNAs that were altered in abundance by exposure to H2S
Summary
Exogenous H2S has dramatic effects on mammalian physiology that can improve survival in changing environmental conditions. The H2Sinduced state enables mice to survive exposure to otherwise lethal hypoxic conditions [2], and improves outcome in rodent models of severe blood loss [3], myocardial infarction [4], aortic occlusion [5] and hepatic ischemia/reperfusion [6]. Increased lifespan and thermotolerance require the conserved sirtuin homologue sir-2.1, though mutant animals with deletions in sir-2.1 grow normally in H2S. The hif-1 transcription factor is required to survive exposure to H2S [8]. Hif is a highly conserved bHLH transcription factor that is wellknown for its role in coordinating the transcriptional response to hypoxia in all animals, including C. elegans [9,10]. The response to H2S involves at least two genes, hif-1 and sir-2.1, which influence lifespan
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