Abstract

description): Ischemia produces translocation of the glucose transport proteins GLUT4 and GLUT1 to the sarcolemma as a critical response to a need for energy. This study proposes to understand the mechanism of this response by using rat papillary muscle in combination with pharmacological tools and an in vivo model of canine ischemia. The hypothesis to be tested is that ischemia triggers activation of AMP kinase, an intracellular protein that is proposed to increase glucose transporters on the sarcolemma. Interaction of AMPK with other signaling pathways will be explored, as well as the role of specific isoforms of AMPK subunits in the heart. The relative roles of exocytosis vs. endocytosis in the process will be evaluated.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL063811-02
Application #
6390563
Study Section
Cardiovascular and Pulmonary Research A Study Section (CVA)
Program Officer
Liang, Isabella Y
Project Start
2000-09-30
Project End
2004-07-31
Budget Start
2001-08-01
Budget End
2002-07-31
Support Year
2
Fiscal Year
2001
Total Cost
$325,209
Indirect Cost

  Institution

Name
Yale University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
082359691
City
New Haven
State
CT
Country
United States
Zip Code
06520

  Publications

Zaha, Vlad G; Qi, Dake; Su, Kevin N et al. (2016) AMPK is critical for mitochondrial function during reperfusion after myocardial ischemia. J Mol Cell Cardiol 91:104-13
Kim, Grace E; Ross, Jenna L; Xie, Chaoqin et al. (2015) LKB1 deletion causes early changes in atrial channel expression and electrophysiology prior to atrial fibrillation. Cardiovasc Res 108:197-208
Qi, Dake; Atsina, Kwame; Qu, Lintao et al. (2014) The vestigial enzyme D-dopachrome tautomerase protects the heart against ischemic injury. J Clin Invest 124:3540-50
Wang, Jingying; Tong, Chao; Yan, Xiaoyan et al. (2013) Limiting cardiac ischemic injury by pharmacological augmentation of macrophage migration inhibitory factor-AMP-activated protein kinase signal transduction. Circulation 128:225-36
Zaha, Vlad G; Young, Lawrence H (2012) AMP-activated protein kinase regulation and biological actions in the heart. Circ Res 111:800-14
Shugrue, Christina A; Alexandre, Martine; Diaz de Villalvilla, Alexander et al. (2012) Cerulein hyperstimulation decreases AMP-activated protein kinase levels at the site of maximal zymogen activation. Am J Physiol Gastrointest Liver Physiol 303:G723-32
Kim, Agnes S; Miller, Edward J; Wright, Tracy M et al. (2011) A small molecule AMPK activator protects the heart against ischemia-reperfusion injury. J Mol Cell Cardiol 51:24-32
Qi, Dake; Hu, Xiaoyue; Wu, Xiaohong et al. (2009) Cardiac macrophage migration inhibitory factor inhibits JNK pathway activation and injury during ischemia/reperfusion. J Clin Invest 119:3807-16
Kim, A S; Miller, E J; Young, L H (2009) AMP-activated protein kinase: a core signalling pathway in the heart. Acta Physiol (Oxf) 196:37-53
Young, Lawrence H (2008) AMP-activated protein kinase conducts the ischemic stress response orchestra. Circulation 117:832-40

Showing the most recent 10 out of 20 publications