Insulin antagonizes AMP-activated protein kinase activation by ischemia or anoxia in rat hearts, without affecting total adenine nucleotides

被引：105

作者：

Beauloye, C

Marsin, AS

Bertrand, L

Krause, U

Hardie, DG

Vanoverschelde, JL

Hue, L

机构：

[1] Inst Cellular Pathol, Hormone & Metab Res Unit, B-1200 Brussels, Belgium

[2] Univ Louvain, Sch Med, Div Cardiol, Brussels, Belgium

[3] Univ Dundee, Wellcome Trust Bioctr, Div Mol Physiol, Dundee DD1 5EH, Scotland

来源：

FEBS LETTERS | 2001年 / 505卷 / 03期

基金：

英国惠康基金;

关键词：

AMP-activated protein kinase; heart ischemia; anoxia; insulin;

D O I：

10.1016/S0014-5793(01)02788-0

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

AMP-activated protein kinase (AMPK) is known to be activated by phosphorylation on Thr172 in response to an increased AMP/ATP ratio. We report here that such an activation indeed occurred in anaerobic rat hearts and that it was antagonized (40-50%) when the hearts were pre-treated with 100 nM insulin. The effect of insulin (1) was blocked by wortmannin, an inhibitor of phosphatidylinositol-3-kinase; (2) only occurred when insulin was added before anoxia, suggesting a hierarchical control; (3) resulted in a decreased phosphorylation state of Thr172 in AMPK and (4) was unrelated to changes in the AMP/ATP ratio. This is the first demonstration that AMPK activity could be changed without a detectable change in the AMP/ATP ratio of the cardiac cell. (C) 2001 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.

引用

收藏

页码：348 / 352

页数：5

相关论文

共 23 条

[1] No-flow ischemia inhibits insulin signaling in heart by decreasing intracellular pH [J].

Beauloye, C ;

Bertrand, L ;

Krause, U ;

Marsin, AS ;

Dresselaers, T ;

Vanstapel, F ;

Vanoverschelde, JL ;

Hue, L .

CIRCULATION RESEARCH, 2001, 88 (05) :513-519

[2]

Bergmeyer H.U., 1984, METHODS ENZYMATIC AN, V6

[3] AMP-activated protein kinase phosphorylation of endothelial NO synthase [J].

Chen, ZP ;

Mitchelhill, KI ;

Michell, BJ ;

Stapleton, D ;

Rodriguez-Crespo, I ;

Witters, LA ;

Power, DA ;

de Montellano, PRO ;

Kemp, BE .

FEBS LETTERS, 1999, 443 (03) :285-289

[4] Characterization of AMP-activated protein kinase γ-subunit isoforms and their role in AMP binding [J].

Cheung, PCF ;

Salt, IP ;

Davies, SP ;

Hardie, DG ;

Carling, D .

BIOCHEMICAL JOURNAL, 2000, 346 :659-669

[5] Effects of wortmannin on insulin- and ischemia-induced stimulation of GLUT4 translocation and FDG uptake in perfused rat hearts [J].

Egert, S ;

Nguyen, N ;

Brosius, FC ;

Schwaiger, M .

CARDIOVASCULAR RESEARCH, 1997, 35 (02) :283-293

[6] Insulin inhibition of 5' adenosine monophosphate-activated protein kinase in the heart results in activation of acetyl coenzyme A carboxylase and inhibition of fatty acid oxidation [J].

Gamble, J ;

Lopaschuk, GD .

METABOLISM-CLINICAL AND EXPERIMENTAL, 1997, 46 (11) :1270-1274

[7] The AMP-activated/SNF1 protein kinase subfamily: Metabolic sensors of the eukaryotic cell? [J].

Hardie, DG ;

Carling, D ;

Carlson, M .

ANNUAL REVIEW OF BIOCHEMISTRY, 1998, 67 :821-855

[8] Characterization of 5'AMP-activated protein kinase activity in the heart and its role in inhibiting acetyl-CoA carboxylase during reperfusion following ischemia [J].

Kudo, N ;

Gillespie, JG ;

Kung, L ;

Witters, LA ;

Schulz, R ;

Clanachan, AS ;

Lopaschuk, GD .

BIOCHIMICA ET BIOPHYSICA ACTA-LIPIDS AND LIPID METABOLISM, 1996, 1301 (1-2) :67-75

[9] Signaling pathway involved in the activation of heart 6-phosphofructo-2-kinase by insulin [J].

Lefebvre, V ;

Mechin, MC ;

Louckx, MP ;

Rider, MH ;

Hue, L .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (37) :22289-22292

[10] Phosphorylation and activation of heart PFK-2 by AMPK has a role in the stimulation of glycolysis during ischaemia [J].

Marsin, AS ;

Bertrand, L ;

Rider, MH ;

Deprez, J ;

Beauloye, C ;

Vincent, MF ;

Van den Berghe, G ;

Carling, D ;

Hue, L .

CURRENT BIOLOGY, 2000, 10 (20) :1247-1255