RRC ID 6384
著者 Khare S, Gomez T, Linster CL, Clarke SG.
タイトル Defective responses to oxidative stress in protein l-isoaspartyl repair-deficient Caenorhabditis elegans.
ジャーナル Mech Ageing Dev
Abstract We have shown that Caenorhabditis elegans lacking the PCM-1 protein repair l-isoaspartyl methyltransferase are more sensitive to oxidative stress than wild-type nematodes. Exposure to the redox-cycling quinone juglone upon exit from dauer diapause results in defective egg-laying (Egl phenotype) in the pcm-1 mutants only. Treatment with paraquat, a redox-cycling dipyridyl, causes a more severe developmental delay at the second larval stage in pcm-1 mutants than in wild-type nematodes. Finally, exposure to homocysteine and homocysteine thiolactone, molecules that can induce oxidative stress via distinct mechanisms, results in a more pronounced delay in development at the first larval stage in pcm-1 mutants than in wild-type animals. Homocysteine treatment also induced the Egl phenotype in mutant but not wild-type nematodes. All of the effects of these agents were reversed upon addition of vitamin C, indicating that the developmental delay and egg-laying defects result from oxidative stress. Furthermore, we have demonstrated that a mutation in the gene encoding the insulin-like receptor DAF-2 suppresses the Egl phenotype in pcm-1 mutants treated with juglone. Our results support a role of PCM-1 in the cellular responses mediated by the DAF-2 insulin-like signaling pathway in C. elegans for optimal protection against oxidative stress.
巻・号 130(10)
ページ 670-80
公開日 2009-10-1
DOI 10.1016/j.mad.2009.08.002
PII S0047-6374(09)00109-2
PMID 19682488
PMC PMC2757507
MeSH Animals Antioxidants / pharmacology Ascorbic Acid / pharmacology Caenorhabditis elegans / drug effects Caenorhabditis elegans / embryology Caenorhabditis elegans / enzymology* Caenorhabditis elegans / genetics Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism Cell Cycle Proteins / genetics Genotype Homocysteine / analogs & derivatives Homocysteine / metabolism Homocysteine / toxicity Larva / metabolism Metamorphosis, Biological Methyltransferases / deficiency* Methyltransferases / genetics Mutation Naphthoquinones / toxicity Oxidants / toxicity Oxidative Stress* / drug effects Oxidative Stress* / genetics Paraquat / toxicity Phenotype Receptor, Insulin / genetics Receptor, Insulin / metabolism
IF 4.304
引用数 20
WOS 分野 GERIATRICS & GERONTOLOGY CELL BIOLOGY
リソース情報
線虫 tm363 tm2679