AMP-activated protein kinase deficiency enhances myocardial ischemia/reperfusion injury but has minimal effect on the antioxidant/antinitrative protection of adiponectin.
BACKGROUND
Diabetes increases the morbidity/mortality of ischemic heart disease, but the underlying mechanisms are incompletely understood. Deficiency of both AMP-activated protein kinase (AMPK) and adiponectin occurs in diabetes, but whether AMPK is cardioprotective or a central mediator of adiponectin cardioprotection in vivo remains unknown.


RESULTS
Male adult mice with cardiomyocyte-specific overexpression of a mutant AMPKalpha2 subunit (AMPK-DN) or wild-type (WT) littermates were subjected to in vivo myocardial ischemia/reperfusion (MI/R) and treated with vehicle or adiponectin. In comparison to WT, AMPK-DN mice subjected to MI/R endured greater cardiac injury (larger infarct size, more apoptosis, and poorer cardiac function) likely as a result of increased oxidative stress in these animals. Treatment of AMPK-DN mice with adiponectin failed to phosphorylate cardiac acetyl-CoA carboxylase as it did in WT mouse heart. However, a significant portion of the cardioprotection of adiponectin against MI/R injury was retained in AMPK-DN mice. Furthermore, treatment of AMPK-DN mice with adiponectin reduced MI/R-induced cardiac oxidative and nitrative stress to the same degree as that seen in WT mice. Finally, treating AMPK-DN cardiomyocytes with adiponectin reduced simulated MI/R-induced oxidative/nitrative stress and decreased cell death (P<0.01).


CONCLUSIONS
Collectively, our results demonstrated that AMPK deficiency significantly increases MI/R injury in vivo but has minimal effect on the antioxidative/antinitrative protection of adiponectin.
Wang
Yajing
Y
Department of Emergency Medicine, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Gao
Erhe
E
Tao
Ling
L
Lau
Wayne Bond
WB
Yuan
Yuexin
Y
Goldstein
Barry J
BJ
Lopez
Bernard L
BL
Christopher
Theodore A
TA
Tian
Rong
R
Koch
Walter
W
Ma
Xin-Liang
XL
D055372:AMP-Activated Protein Kinases / Q000172:deficiency* / Q000235:genetics; D052242:Adiponectin / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D016923:Cell Death; D008297:Male; D051379:Mice; D009154:Mutation; D015428:Myocardial Reperfusion Injury / Q000209:etiology*; D032383:Myocytes, Cardiac; D009566:Nitrates; D009569:Nitric Oxide; D018384:Oxidative Stress
D052242:Adiponectin; D000975:Antioxidants; D009566:Nitrates; D009569:Nitric Oxide; D055372:AMP-Activated Protein Kinases