Genome-Wide Expression Profiling of Anoxia/Reoxygenation in Rat Cardiomyocytes Uncovers the Role of MitoKATP in Energy Homeostasis.

Abstract

Mitochondrial ATP-sensitive potassium channel (mitoK(ATP)) is a common end effector of many protective stimuli in myocardial ischemia-reperfusion injury (MIRI). However, the specific molecular mechanism underlying its myocardial protective effect is not well elucidated. We characterized an anoxia/reoxygenation (A/R) model using freshly isolated adult rat cardiomyocytes. MitoK(ATP) status was interfered with its specific opener diazoxide (DZ) or blocker 5-hydroxydecanote (5-HD). Digital gene expression (DGE) and bioinformatic analysis were deployed. Three energy metabolism related genes (MT-ND6, Idh2, and Acadl) were upregulated when mitoK(ATP) opened. In addition, as many as 20 differentially expressed genes (DEGs) were significantly enriched in five energy homeostasis correlated pathways (PPAR, TCA cycle, fatty acid metabolism, and peroxisome). These findings indicated that mitoK(ATP) opening in MIRI resulted in energy mobilization, which was confirmed by measuring ATP content in cardiomyocytes. These causal outcomes could be a molecular mechanism of myocardial protection of mitoKATP and suggested that the mitoK(ATP) opening plays a physiologic role in triggering cardiomyocytes' energy homeostasis during MIRI. Strategies of modulating energy expenditure during myocardial ischemia-reperfusion may be promising approaches to reduce MIRI.

• Authors: Song Cao, Yun Liu, Wenting Sun, Li Zhao, Lin Zhang, Xinkui Liu, Tian Yu
• Journal: Oxidative medicine and cellular longevity (Oxid Med Cell Longev) Vol. 2015 Pg. 756576 ( 2015) ISSN: 1942-0994 [Electronic] United States
• PMID: 26171116 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Decanoic Acids
• Hydroxy Acids
• Potassium Channels
• mitochondrial K(ATP) channel
• 5-hydroxydecanoic acid
• Adenosine Triphosphate
• Isocitrate Dehydrogenase
• Acyl-CoA Dehydrogenase
• NADH Dehydrogenase
• Diazoxide
• Calcium

Topics

• Acyl-CoA Dehydrogenase (genetics, metabolism)
• Adenosine Triphosphate (metabolism)
• Animals
• Calcium (metabolism)
• Cell Survival (drug effects)
• Decanoic Acids (pharmacology)
• Diazoxide (pharmacology)
• Energy Metabolism (genetics)
• Gene Expression Profiling
• Genome
• Hydroxy Acids (pharmacology)
• Hypoxia
• Isocitrate Dehydrogenase (genetics, metabolism)
• Male
• Mitochondria (metabolism)
• Myocytes, Cardiac (cytology, drug effects, metabolism)
• NADH Dehydrogenase (genetics, metabolism)
• Potassium Channels (chemistry, metabolism)
• Rats
• Rats, Sprague-Dawley
• Real-Time Polymerase Chain Reaction