title: Anti-apoptotic signaling as a cytoprotective mechanism in mammalian hibernation.
abstract: In the context of normal cell turnover, apoptosis is a natural phenomenon involved in making essential life and death decisions. Apoptotic pathways balance signals which promote cell death (pro-apoptotic pathways) or counteract these signals (anti-apoptotic pathways). We proposed that changes in anti-apoptotic proteins would occur during mammalian hibernation to aid cell preservation during prolonged torpor under cellular conditions that are highly injurious to most mammals (e.g. low body temperatures, ischemia). Immunoblotting was used to analyze the expression of proteins associated with pro-survival in six tissues of thirteen-lined ground squirrels, Ictidomys tridecemlineatus. The brain showed a concerted response to torpor with significant increases in the levels of all anti-apoptotic targets analyzed (Bcl-2, Bcl-xL, BI-1, Mcl-1, cIAP1/2, xIAP) as well as enhanced phosphorylation of Bcl-2 at S70 and T56. Heart responded similarly with most anti-apoptotic proteins elevated significantly during torpor except for Bcl-xL and xIAP that decreased and Mcl-1 that was unaltered. In liver, BI-1 increased whereas cIAP1/2 decreased. In kidney, there was an increase in BI-1, cIAP and xIAP but decreases in Bcl-xL and p-Bcl-2(T56) content. In brown adipose tissue, protein levels of BI-1, cIAP1/2, and xIAP decreased significantly during torpor (compared with euthermia) whereas Bcl-2, Bcl-xL, Mcl-1 were unaltered; however, Bcl-2 showed enhanced phosphorylation at Thr56 but not at Ser70. In skeletal muscle, only xIAP levels changed significantly during torpor (an increase). The data show that anti-apoptotic pathways have organ-specific responses in hibernators with a prominent potential role in heart and brain where coordinated enhancement of anti-apoptotic proteins occurred in response to torpor.
authors: Institute of Biochemistry & Department of Biology, Carleton University, Ottawa, Ontario, Canada K1S 5B6.
authors: Andrew N
authors: AN
authors: Rouble
authors: Institute of Biochemistry & Department of Biology, Carleton University, Ottawa, Ontario, Canada K1S 5B6.
authors: Joshua
authors: J
authors: Hefler
authors: Institute of Biochemistry & Department of Biology, Carleton University, Ottawa, Ontario, Canada K1S 5B6.
authors: Hapsatou
authors: H
authors: Mamady
authors: Institute of Biochemistry & Department of Biology, Carleton University, Ottawa, Ontario, Canada K1S 5B6.
authors: Kenneth B
authors: KB
authors: Storey
authors: Institute of Biochemistry & Department of Biology, Carleton University, Ottawa, Ontario, Canada K1S 5B6.
authors: Shannon N
authors: SN
authors: Tessier
keywords: Anti-apoptosis; Bcl proteins; Cytoprotection; Hibernation; Inhibitor of apoptosis proteins
references: Cell Cycle. 2012 May 1;11(9):1714-26
references: 22510572
references: Nat Cell Biol. 2000 Sep;2(9):E163-5
references: 10980714
references: Fed Proc. 1980 Oct;39(12):2969-73
references: 6998740
references: J Exp Biol. 2002 Jun;205(Pt 11):1625-31
references: 12000807
references: Apoptosis. 2010 Mar;15(3):350-64
references: 20238476
references: Adv Clin Chem. 2010;52:77-108
references: 21275340
references: Toxicol Appl Pharmacol. 2008 Apr 1;228(1):93-104
references: 18201741
references: Experientia. 1996 Oct 31;52(10-11):1008-17
references: 8917732
references: Comp Biochem Physiol A Mol Integr Physiol. 2009 Jun;153(2):213-21
references: 19233307
references: Science. 2004 Jul 30;305(5684):626-9
references: 15286356
references: Am Heart J. 1955 Mar;49(3):367-84
references: 14349852
references: Curr Pharm Des. 2011;17(3):246-55
references: 21348826
references: Adv Exp Med Biol. 2012;942:157-83
references: 22399422
references: Apoptosis. 2010 Mar;15(3):331-49
references: 20033783
references: Nat Rev Cancer. 2010 Aug;10(8):561-74
references: 20651737
references: Apoptosis. 2010 Mar;15(3):293-312
references: 20043212
references: Apoptosis. 2009 Aug;14(8):950-60
references: 19495985
references: Physiol Genomics. 2008 Jan 17;32(2):170-81
references: 17925484
references: J Cereb Blood Flow Metab. 1994 Mar;14(2):193-205
references: 8113316
references: Transplantation. 2011 Dec 15;92(11):1215-21
references: 22082817
references: J Comp Physiol B. 2010 Jun;180(5):775-83
references: 20112024
references: PLoS One. 2011 Mar 04;6(3):e17574
references: 21394211
references: J Biol Chem. 1997 Jul 25;272(30):19022-6
references: 9228085
references: Proc Natl Acad Sci U S A. 2000 Feb 15;97(4):1578-83
references: 10677502
references: Cell Death Differ. 2007 Sep;14(9):1617-27
references: 17510660
references: Naturwissenschaften. 2007 Feb;94(2):77-99
references: 17039344
references: Mol Cell. 2010 Feb 12;37(3):299-310
references: 20159550
references: Arch Biochem Biophys. 2008 Sep 1;477(1):77-85
references: 18541136
references: J Exp Biol. 2007 May;210(Pt 10):1700-14
references: 17488933
references: Mol Cell. 2004 Aug 13;15(3):355-66
references: 15304216
references: J Biol Chem. 2000 Jul 14;275(28):21661-7
references: 10766756
references: Cell Calcium. 2011 Sep;50(3):251-60
references: 21663964
references: Methods Cell Biol. 2012;107:295-320
references: 22226528
references: Gerontology. 2010;56(2):220-30
references: 19602865
references: Proc Natl Acad Sci U S A. 2004 Jan 6;101(1):153-8
references: 14660795
references: EMBO J. 2011 Aug 23;30(18):3667-83
references: 21863020
references: Cryobiology. 2000 Jun;40(4):332-42
references: 10924265
references: Nat Cell Biol. 2000 Aug;2(8):476-83
references: 10934467
references: Cell Death Differ. 2011 Aug;18(8):1271-8
references: 21597463
references: Physiol Genomics. 2005 Oct 17;23(2):227-34
references: 16076930
references: Biochem Biophys Res Commun. 1999 Jan 19;254(2):424-9
references: 9918854
references: Biochimie. 2002 Feb-Mar;84(2-3):203-14
references: 12022951
references: Science. 1986 Jan 17;231(4735):234-41
references: 2417316
references: Med Sci Sports Exerc. 2009 Oct;41(10):1876-86
references: 19727026
references: Proc Natl Acad Sci U S A. 1999 Mar 30;96(7):3775-80
references: 10097113
references: Comp Biochem Physiol B Biochem Mol Biol. 2008 Feb;149(2):388-93
references: 18055242
references: Mol Cell Biochem. 2006 Nov;292(1-2):89-98
references: 16788740
references: Apoptosis. 2010 Mar;15(3):386-99
references: 20127173
references: Leukemia. 2001 Apr;15(4):515-22
references: 11368354
references: Biochemistry (Mosc). 2001 Aug;66(8):918-25
references: 11566064
references: Science. 2005 Oct 7;310(5745):66-7
references: 16210526
references: J Comp Physiol B. 2010 Aug;180(6):927-34
references: 20352231
references: Biol Rev Camb Philos Soc. 2004 Feb;79(1):207-33
references: 15005178
references: J Biol Chem. 1997 May 2;272(18):11671-3
references: 9115213