Molecular basis for oxidative stress induced by simulated microgravity in nematode Caenorhabditis elegans

Caenorhabditis elegans is an important in vivo assay system for toxicological studies. Herein, we investigated the role of oxidative stress and the underlying molecular mechanism for induced adverse effects of simulated microgravity. In nematodes, simulated microgravity treatment induced a significant induction of oxidative stress. Genes (mev-1, gas-1, and isp-1) encoding a molecular machinery for the control of oxidative stress were found to be dysregulated in simulated microgravity treated nematodes. Meanwhile, genes (sod-2, sod-3, sod-4, sod-5, aak-2, skn-1, and gst-4) encoding certain antioxidant defense systems were increased in simulated microgravity treated nematodes. Mutation of mev-1, gas-1, sod-2, sod-3, aak-2, skn-1, or gst-4 enhanced susceptibility to oxidative stress induced by simulated microgravity, whereas mutation of isp-1 induced a resistance to oxidative stress induced by simulated microgravity. Mutation of sod-2, sod-3, or aak-2 further suppressed the recovery effect of simulated microgravity toxicity in nematodes after simulated microgravity treatment for 1h. Moreover, administration of ascorbate could inhibit the adverse effects including the induction of oxidative stress in simulated microgravity treated nematodes. Mutation of any of the genes encoding metallothioneins or the genes of hsp-16.1, hsp-16.2 and hsp-16.48 encoding heat-shock proteins did not affect the induction of oxidative stress in simulated microgravity treated nematodes. Our results provide a molecular basis for the induction of oxidative stress in simulated microgravity treated organisms.