title: Defective responses to oxidative stress in protein l-isoaspartyl repair-deficient Caenorhabditis elegans.
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.
authors.affiliation: Department of Chemistry and Biochemistry and the Molecular Biology Institute, University of California, Los Angeles, CA 90095, USA.
authors.forename: Shilpi
authors.initials: S
authors.lastname: Khare
authors.forename: Tara
authors.initials: T
authors.lastname: Gomez
authors.forename: Carole L
authors.initials: CL
authors.lastname: Linster
authors.forename: Steven G
authors.initials: SG
authors.lastname: Clarke
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001205:Ascorbic Acid / Q000494:pharmacology; D017173:Caenorhabditis elegans / Q000187:drug effects / Q000196:embryology / Q000201:enzymology* / Q000235:genetics; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000235:genetics; D005838:Genotype; D006710:Homocysteine / Q000031:analogs & derivatives / Q000378:metabolism / Q000633:toxicity; D007814:Larva / Q000378:metabolism; D008675:Metamorphosis, Biological; D008780:Methyltransferases / Q000172:deficiency* / Q000235:genetics; D009154:Mutation; D009285:Naphthoquinones / Q000633:toxicity; D016877:Oxidants / Q000633:toxicity; D018384:Oxidative Stress / Q000187:drug effects / Q000235:genetics; D010269:Paraquat / Q000633:toxicity; D010641:Phenotype; D011972:Receptor, Insulin / Q000235:genetics / Q000378:metabolism
chemical_list: D000975:Antioxidants; D029742:Caenorhabditis elegans Proteins; D018797:Cell Cycle Proteins; D009285:Naphthoquinones; D016877:Oxidants; D006710:Homocysteine; C007957:homocysteine thiolactone; C490112:pcm-1 protein, C elegans; D008780:Methyltransferases; C107483:DAF-2 protein, C elegans; D011972:Receptor, Insulin; D010269:Paraquat; D001205:Ascorbic Acid; C005134:juglone
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