Oxidation resistance 1 is essential for protection against oxidative stress and participates in the regulation of aging in Caenorhabditis elegans

Abstract

Human oxidation resistance 1 (OXR1) functions in protection against oxidative damage and its homologs are highly conserved in eukaryotes examined so far, but its function still remains uncertain. In this study, we identified a homolog (LMD-3) of human OXR1 in the nematode Caenorhabditis elegans (C. elegans). The expressed LMD-3 was able to suppress the mutator phenotypes of E. coli mutMmutY and mutT mutants. Purified LMD-3 did not have enzymatic activity against 8-oxoG, superoxide dismutase (SOD), or catalase activities. Interestingly, the expression of LMD-3 was able to suppress the methyl viologen or menadione sodium bisulfite-induced expression of soxS and sodA genes in E. coli. The sensitivity of the C. elegans lmd-3 mutant to oxidative and heat stress was markedly higher than that of the wild-type strain N2. These results suggest that LMD-3 protects cells against oxidative stress. Furthermore, we found that the lifespan of the C. elegans lmd-3 mutant was significantly reduced compared with that of the N2, which was resulted from the acceleration of aging. We further examined the effects of deletions in other oxidative defense genes on the properties of the lmd-3 mutant. The deletion of sod-2 and sod-3, which are mitochondrial SODs, extended the lifespan of the lmd-3 mutant. These results indicate that, in cooperation with mitochondrial SODs, LMD-3 contributes to the protection against oxidative stress and aging in C. elegans.

Keywords::

• LMD-3
• OXR1
• aging
• nematode
• oxidative stress

Declaration of interest

The authors report no declarations of interest. The authors alone are responsible for the content and writing of the paper.

This work was supported by Grants-in-Aid for Scientific Research (#24510071) from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan (to Q.-M.Z.-A.), and the Grants for Excellent Graduate Schools program (MEXT). The authors thank Dr. Elizabeth Nakajima for critically reading the manuscript. We are also grateful to the Shiseido Female Research Science Grant for supporting Q.-M.Z.-A. Some strains were provided by the CGC, which is funded by the NIH Office of Research Infrastructure Programs (P40 OD010440). The plasmid pTrc99A/hOXR1 was kindly provided by Dr. Kazunari Hashiguchi (National Institute of Biomedical Innovation).