Defective responses to oxidative stress in protein l-isoaspartyl repair-deficient Caenorhabditis elegans.
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.
Khare
Shilpi
S
Department of Chemistry and Biochemistry and the Molecular Biology Institute, University of California, Los Angeles, CA 90095, USA.
Gomez
Tara
T
Linster
Carole L
CL
Clarke
Steven G
SG
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
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
Clin Chem Lab Med. 2007;45(12):1704-16
17937605
Dev Biol. 2007 Mar 15;303(2):493-500
17187774
Mol Neurobiol. 2007 Feb;35(1):85-94
17519507
Eur J Biochem. 2000 Jul;267(14):4397-405
10880963
J Gerontol A Biol Sci Med Sci. 2008 Aug;63(8):798-808
18772467
WormBook. 2006 Oct 13;:1-25
18050432
Free Radic Biol Med. 2005 Jun 1;38(11):1518-25
15890626
J Biol Chem. 1988 Jan 25;263(3):1386-90
3335550
Methods Cell Biol. 1995;48:3-29
8531730
Mech Ageing Dev. 2008 Dec;129(12):752-8
18977240
Genetics. 1983 Aug;104(4):619-47
11813735
Proc Natl Acad Sci U S A. 1984 Feb;81(3):819-23
6583682
Dev Cell. 2004 Apr;6(4):577-88
15068796
Nature. 2003 Jul 17;424(6946):277-83
12845331
J Cell Physiol. 2008 Mar;214(3):721-9
17894411
J Clin Invest. 1986 Apr;77(4):1370-6
3514679
Free Radic Biol Med. 2004 Jul 15;37(2):139-45
15203185
Int J Biochem Cell Biol. 2004 Oct;36(10):1919-32
15203107
Ageing Res Rev. 2003 Jul;2(3):263-85
12726775
Mech Ageing Dev. 2002 Nov;123(12):1579-87
12470895
Arch Biochem Biophys. 1997 Dec 15;348(2):320-8
9434744
Mech Ageing Dev. 1988 Apr;43(1):71-8
3374177
Free Radic Biol Med. 2005 Apr 1;38(7):908-19
15749387
PLoS One. 2008 Sep 22;3(9):e3258
18806875
Eur J Biochem. 2002 Apr;269(8):2032-9
11985579
Genetics. 1989 Apr;121(4):703-21
2721931
Proc Natl Acad Sci U S A. 2001 Dec 18;98(26):14814-8
11742076
FASEB J. 1999 Aug;13(11):1385-93
10428762
Dev Biol. 1975 Oct;46(2):326-42
1183723
Amino Acids. 2003 Dec;25(3-4):409-17
14661100
J Gerontol A Biol Sci Med Sci. 1995 Nov;50(6):B322-6
7583787
J Gerontol A Biol Sci Med Sci. 2002 Mar;57(3):B109-14
11867647
J Biol Chem. 2006 Nov 3;281(44):33802-13
16959769
Nature. 1997 Oct 30;389(6654):994-9
9353126
Biosci Biotechnol Biochem. 2005 Oct;69(10):2015-8
16244463
Mech Ageing Dev. 1993 May;68(1-3):1-10
8350650
Aging Cell. 2005 Feb;4(1):1-12
15659208
Aging Cell. 2006 Feb;5(1):31-7
16441841
Mech Ageing Dev. 2001 May 31;122(7):673-93
11322992
Aging Cell. 2003 Apr;2(2):111-21
12882324
Antioxid Redox Signal. 2005 May-Jun;7(5-6):752-60
15890021
Genetics. 2007 Jul;176(3):1567-77
17483415
Arch Biochem Biophys. 1983 Apr 1;222(1):35-43
6687666
Aging Cell. 2008 Jan;7(1):13-22
17996009
Mutat Res. 1996 Oct 28;358(1):1-6
8921971