title: The Mammalian circadian clock gene per2 modulates cell death in response to oxidative stress.
abstract: Living in the earth's oxygenated environment forced organisms to develop strategies to cope with the damaging effects of molecular oxygen known as reactive oxygen species (ROS). Here, we show that Per2, a molecular component of the mammalian circadian clock, is involved in regulating a cell's response to oxidative stress. Mouse embryonic fibroblasts (MEFs) containing a mutation in the Per2 gene are more resistant to cytotoxic effects mediated by ROS than wild-type cells, which is paralleled by an altered regulation of bcl-2 expression in Per2 mutant MEFs. The elevated survival rate and alteration of NADH/NAD(+) ratio in the mutant cells is reversed by introduction of the wild-type Per2 gene. Interestingly, clock synchronized cells display a time dependent sensitivity to paraquat, a ROS inducing agent. Our observations indicate that the circadian clock is involved in regulating the fate of a cell to survive or to die in response to oxidative stress, which could have implications for cancer development and the aging process.
authors: Department of Biology, Division of Biochemistry, University of Fribourg , Fribourg , Switzerland.
authors: Maria Chiara
authors: MC
authors: Magnone
authors: Department of Biology, Division of Biochemistry, University of Fribourg , Fribourg , Switzerland.
authors: Sonja
authors: S
authors: Langmesser
authors: Department of Biology, Division of Biochemistry, University of Fribourg , Fribourg , Switzerland.
authors: April Candice
authors: AC
authors: Bezdek
authors: Department of Biology, Division of Biochemistry, University of Fribourg , Fribourg , Switzerland.
authors: Tiziano
authors: T
authors: Tallone
authors: Department of Biology, Division of Biochemistry, University of Fribourg , Fribourg , Switzerland.
authors: Sandro
authors: S
authors: Rusconi
authors: Department of Biology, Division of Biochemistry, University of Fribourg , Fribourg , Switzerland.
authors: Urs
authors: U
authors: Albrecht
keywords: SIN-1; UV; adenovirus; apoptosis; bcl-2; p53; paraquat; plumbagin
references: Mol Metab. 2013 May 10;2(3):184-93
references: 24049733
references: Science. 2009 May 1;324(5927):651-4
references: 19299583
references: Nature. 2002 Aug 29;418(6901):935-41
references: 12198538
references: Biochem J. 1967 May;103(2):514-27
references: 4291787
references: Cold Spring Harb Symp Quant Biol. 2011;76:31-8
references: 22179986
references: J Cell Physiol. 2003 May;195(2):158-67
references: 12652643
references: Cell. 2001 Jul 27;106(2):141-3
references: 11511342
references: J Biol Chem. 2004 Feb 27;279(9):7512-20
references: 14660625
references: J Biol Chem. 1995 Jun 2;270(22):13399-405
references: 7768942
references: Cell Death Differ. 2003 Aug;10(8):889-98
references: 12867996
references: Proc Natl Acad Sci U S A. 2001 Jan 30;98(3):1188-93
references: 11158615
references: Chronobiol Int. 2003 Nov;20(6):921-62
references: 14680136
references: Science. 2009 May 1;324(5927):654-7
references: 19286518
references: Mol Cell Biochem. 2010 Feb;335(1-2):37-45
references: 19714448
references: Anal Biochem. 1965 Apr;11:1-5
references: 14328641
references: Biochem Biophys Res Commun. 2003 Jan 31;301(1):222-4
references: 12535666
references: Pathol Oncol Res. 2010 Sep;16(3):403-11
references: 19957060
references: Cell. 1998 Jun 12;93(6):929-37
references: 9635423
references: Chronobiol Int. 2009 Dec;26(8):1514-44
references: 20030538
references: Science. 2001 Jul 20;293(5529):510-4
references: 11441146
references: Cancer Sci. 2006 Jul;97(7):589-96
references: 16827798
references: Science. 2000 Sep 29;289(5488):2344-7
references: 11009419
references: Nature. 2004 Mar 25;428(6981):431-7
references: 15042092
references: Annu Rev Physiol. 1993;55:16-54
references: 8466172
references: J Biol Rhythms. 2001 Apr;16(2):100-4
references: 11302552
references: Cell. 2002 Oct 4;111(1):41-50
references: 12372299
references: Cell. 2002 May 3;109(3):307-20
references: 12015981
references: Int J Cell Biol. 2010;2010:214074
references: 20182529
references: EMBO J. 2002 May 1;21(9):2180-8
references: 11980715
references: Annu Rev Physiol. 2001;63:695-728
references: 11181973
references: Nature. 1999 Jul 8;400(6740):169-73
references: 10408444
references: J Biol Chem. 1969 Nov 25;244(22):6049-55
references: 5389100
references: Nat Rev Neurosci. 2003 Aug;4(8):649-61
references: 12894240
references: Science. 2002 Mar 8;295(5561):1895-7
references: 11847309
references: Nat Commun. 2013;4:2444
references: 24051492
references: Genes Dev. 2002 Oct 15;16(20):2633-8
references: 12381662
references: World J Gastroenterol. 2003 Aug;9(8):1781-5
references: 12918120
references: Ann N Y Acad Sci. 1984;423:442-68
references: 6588808
references: Proc Natl Acad Sci U S A. 1994 Dec 6;91(25):12248-52
references: 7991614
references: Neuron. 2001 Nov 20;32(4):657-71
references: 11719206
references: Anticancer Res. 2009 Apr;29(4):1201-9
references: 19414365
references: Anal Biochem. 1995 Oct 10;231(1):218-24
references: 8678304
references: Cytometry. 1992;13(6):615-20
references: 1451593
references: Cell. 2002 Jul 26;110(2):251-60
references: 12150932
references: Mol Carcinog. 2004 Aug;40(4):201-11
references: 15264212
references: J Biol Chem. 1999 Sep 3;274(36):25869-76
references: 10464329
references: Pathol Biol (Paris). 2003 Jun;51(4):216-9
references: 12852994