The Response of Caenorhabditis elegans to Hydrogen Sulfide and Hydrogen Cyanide.

Publication Type:

Journal Article

Source:

Genetics, Volume 189, Issue 2, p.521-32 (2011)

Keywords:

2011, Amino Acid Sequence, Animals, Animals, Genetically Modified, Antibody Development Core Facility, Basic Sciences Division, Blotting, Western, Caenorhabditis elegans, Center-Authored Paper, Cysteine Synthase, Dioxygenases, Disease Resistance, Female, Green Fluorescent Proteins, Host-Pathogen Interactions, Hydrogen Cyanide Hypoxia-Inducible Factor 1, Male, Microscopy, Confocal, Molecular Sequence Data, Mutation, Pseudomonas aeruginosa, Quinone Reductases, Research Trials Office Core Facility - Biostatistics Service, Reverse Transcriptase Polymerase Chain Reaction, RNA Interference, Scientific Imaging Core Facility, September 2011, Sequence Homology, Amino Acid, Shared Resources

Abstract:

Hydrogen sulfide (H(2)S), an endogenously produced small molecule, protects animals from various stresses. Recent studies in demonstrate that animals exposed to H(2)S are long-lived, resistant to hypoxia and resistant to ischemia-reperfusion injury. We performed a forward genetic screen to gain insights into the molecular mechanisms Caenorhabditis elegans uses to appropriately respond to H(2)S. At least two distinct pathways appear to be important for this response including the H(2)S-oxidation pathway and the hydrogen cyanide (HCN)-assimilation pathway.The H(2)S-oxidation pathway, requires two distinct enzymes important for the oxidation of H(2)S; the sulfide:quinone reductase, sqrd-1, and the dioxygenase ethe-1. The hydrogen cyanide (HCN)-assimilation pathway, requires the cysteine synthase homologs cysl-1 and cysl-2. A low dose of either H(2)S or HCN can activate hypoxia-inducible-factor (HIF)-1, which is required for C. elegans to respond to either gas. sqrd-1 and cysl-2 represent the entry points in the H(2)S-oxidation and HCN-assimilation pathways, respectively, and expression of both of these enzymes is highly induced by HIF-1 in response to both H(2)S and HCN. In addition their role in appropriately responding to H(2)S and HCN, we found that cysl-1 and cysl-2 are both essential mediators of innate immunity against fast-paralytic-killing by Pseudomonas. Furthermore, in agreement with these data, we showed that growing worms in the presence of H(2)S is sufficient to confer resistance to Pseudomonas fast-paralytic-killing. Our results suggest the hypoxia-independent hif-1 response in C. elegans evolved to respond to the naturally occurring small molecules H(2)S and HCN.