The effect of aging on mitochondrial and cytosolic hepatic intrinsic death pathway and apoptosis associated proteins in Fischer 344 rats

被引：9

作者：

Mach, John ^{[1
,2
,3
,4
]}

Huizer-Pajkos, Aniko ^{[1
,2
,3
]}

Kane, Alice ^{[1
,2
,3
,4
]}

Jones, Brett ^{[1
,4
,5
]}

McKenzie, Catriona ^{[6
]}

Mitchell, Sarah J. ^{[11
]}

de Cabo, Rafael ^{[11
]}

Cogger, Victoria C. ^{[4
,7
,8
,9
,10
]}

Le Couteur, David G. ^{[4
,7
,8
,9
,10
]}

Hilmer, Sarah N. ^{[1
,2
,3
,4
]}

机构：

[1] Kolling Inst Med Res, Lab Ageing & Pharmacol, Sydney, NSW, Australia

[2] Royal N Shore Hosp, Dept Clin Pharmacol, Sydney, NSW, Australia

[3] Royal N Shore Hosp, Dept Aged Care, Sydney, NSW, Australia

[4] Univ Sydney, Sydney Med Sch, Sydney, NSW 2006, Australia

[5] Royal N Shore Hosp, Dept Gastroenterol, Sydney, NSW, Australia

[6] Royal Prince Alfred Hosp, Dept Pathol, Sydney, NSW, Australia

[7] Concord Hosp, Ageing & Alzheimers Inst, Concord, NSW, Australia

[8] Concord Hosp, Ctr Educ & Res Ageing, Concord, NSW, Australia

[9] Univ Sydney, Sydney, NSW 2006, Australia

[10] Concord Hosp, ANZAC Res Inst, Concord, NSW, Australia

[11] NIA, Translat Gerontol Branch, NIH, Baltimore, MD 21224 USA

来源：

EXPERIMENTAL GERONTOLOGY | 2015年 / 67卷

基金：

英国医学研究理事会; 美国国家卫生研究院;

关键词：

Aging; Liver; Apoptosis; Mitochondria; Intrinsic death pathway; LIVER-DISEASE; CYTOCHROME-C; CELL-DEATH; BCL-2; BAX; MECHANISMS; BCL-X(L); FAMILY; INJURY;

D O I：

10.1016/j.exger.2015.04.009

中图分类号：

R592 [老年病学]; C [社会科学总论];

学科分类号：

03 ; 0303 ; 100203 ;

摘要：

Apoptosis is increased in the liver in old age and is a common pathological feature of liver disease. The mitochondria play a key role in regulating apoptosis via the intrinsic death pathway. As the effect of aging on this pathway is unclear, we aimed to characterize the impact of aging on the hepatic intrinsic death pathway and apoptosis. Livers from young adult (6.6 +/- 0.3 months, n = 9) and old (25.4 +/- 0.7 months, n = 9) male Fischer 344 rats were extracted for cellular fractionation and immunobloting. In old age there were lower mitochondrial protein levels of pro-apoptotic BAK, BID, tBID and VDAC1 (p < 0.05) and of anti-apoptotic Bcl-2. Compared to young, old rats had lower cytosolic protein levels of pro-apoptotic BAX, BAK, BID, tBID and anti-apoptotic Bcl-xL (p < 0.05). BAK, Bcl-2 and Bcl-xL were found in the cytosol. Furthermore with old age, cytosolic protein levels of cytochrome C, AIF and cleaved caspase-9 did not change but activation of caspase-3, -6 and -7 increased (p < 0.05) and DNA fragmentation trended to increase. Our results suggest an age-related decline in the levels of a number of proteins involved in the intrinsic death pathway, an uncoupling of intermediate apoptosis signaling and increased cellular apoptosis in the liver in old age. (C) 2015 Elsevier Inc. All rights reserved.

引用

页码：54 / 61

页数：8

共 44 条

[1] Dietary Fat and Aging Modulate Apoptotic Signaling in Liver of Calorie-Restricted Mice [J].