title: Ischemia elicits a coordinated expression of pro-survival proteins in mouse myocardium.
abstract: Cardiomyocytes are post-mitotic, long-lived cells until disruptions to pro-survival factors occur after myocardial ischemia. To gain an understanding of the factors involved with ischemic injury, we examined expression changes in pro-survival and opposing pro-apoptotic signals at early and chronic periods of ischemia using an in vivo murine model. Alterations of pro-survival proteins such as the inhibitor of apoptosis protein on chromosome X (xIAP) and the apoptotic repressor protein (ARC) have not been evaluated in a murine model of cardiac ischemia. Early ischemia (1 day) resulted in a 50% reduction in ARC protein levels relative to sham-operated left ventricles, without significant changes in the expression of xIAP or other pro-survival factors. In contrast, a deficiency of xIAP expression was found in cardiac infarcts starting after 1 week, concomitant with significant evidence of apoptotic cell death and an up-regulation of pro-apoptotic signals including Bax, tumor necrosis factor-a, and caspase-8 activation. Chronic ischemia (after 2 weeks) was associated with elevated levels of other pro-survival factors such as Bcl-xL and the phosphorylated form of Akt, as part of the adaptive remodeling of the myocardium. Altogether, these findings suggest that strategies to increase IAP expression may promote myocyte survival after chronic ischemia.
authors.affiliation: Department of Microbiology, Biochemistry and Immunology, Morehouse School of Medicine, 720 Westview Drive, Atlanta, GA 30310, USA. Lyn@msm.edu
authors.forename: Deborah
authors.initials: D
authors.lastname: Lyn
authors.forename: Shaojia
authors.initials: S
authors.lastname: Bao
authors.forename: Nicole A
authors.initials: NA
authors.lastname: Bennett
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Liu
authors.forename: Nerimiah L
authors.initials: NL
authors.lastname: Emmett
mesh_terms: D000208:Acute Disease; D000818:Animals; D051017:Apoptosis Regulatory Proteins; D051023:BH3 Interacting Domain Death Agonist Protein; D015153:Blotting, Western; D002352:Carrier Proteins / Q000378:metabolism; D020169:Caspases / Q000378:metabolism; D002470:Cell Survival; D002908:Chronic Disease; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009124:Muscle Proteins / Q000378:metabolism; D017202:Myocardial Ischemia / Q000378:metabolism* / Q000473:pathology*; D009206:Myocardium / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D051636:X-Linked Inhibitor of Apoptosis Protein; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein
chemical_list: D051017:Apoptosis Regulatory Proteins; D051023:BH3 Interacting Domain Death Agonist Protein; C494827:Bax protein, mouse; C494812:Bcl2l1 protein, mouse; C494815:Bid protein, mouse; D002352:Carrier Proteins; D009124:Muscle Proteins; C491787:Nol3 protein, mouse; D011506:Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D014409:Tumor Necrosis Factor-alpha; D051636:X-Linked Inhibitor of Apoptosis Protein; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; D020169:Caspases