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KMID : 1034820190150040415
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Molecular & Cellular Toxicology
2019 Volume.15 No. 4 p.415 ~ p.424
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Sphingosine kinase and p38 MAP kinase signaling promote resistance to arsenite-induced lethality in Caenorhabditis elegan
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Kim Sung-Jin
Sieburth Derek
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Abstract
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Backgrounds: Arsenite is a naturally occurring mitochondrial toxin that generates oxidative stress in vivo. Previously, we have reported that SPHK-1/sphingosine kinase plays a critical role in promoting survival following arsenite exposure in C. elegans. However, the molecular mechanism by which SPHK-1 confers resistance to arsenite-induced toxicity is not known.
Methods: Using a combination of genetic, fluorescence imaging, and behavioral approaches, we addressed the cellular and molecular mechanism by which SPHK-1 signaling protects animals from arsenite-induced lethality.
Results: SPHK-1 kinase activity and localization to mitochondria are required for protection from arsenite-induced lethality. Genetic alterations leading to low SPH levels promote resistance to arsenite-mediated toxicity. SPHK-1 functions in the PMK-1/p38 MAPK pathways in the intestine to promote protection. Finally, sphk-1 mutants are sensitive to a range of oxidative stressors including juglone, paraquat and heat.
Conclusion: SPHK-1 and PMK-1 signaling play important roles in the oxidative stress response in C. elegans.
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KEYWORD
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Sphingosine kinase, Oxidative stress, PMK-1, SKN-1
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