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Sphingosine kinase and p38 MAP kinase signaling promote resistance to arsenite-induced lethality in Caenorhabditis elegan

Molecular & Cellular Toxicology 2019년 15권 4호 p.415 ~ 424
 ( Kim Sung-Jin ) - University of Southern California Keck School of Medicine Zilkha Neurogenetic Institute

 ( Sieburth Derek ) - University of Southern California Keck School of Medicine Zilkha Neurogenetic Institute


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.


Sphingosine kinase; Oxidative stress; PMK-1; SKN-1
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