Molecular mechanisms responsible for alcohol-induced myopathy in skeletal muscle and heart

Abstract

Chronic alcohol abuse has the potential to modulate striated muscle physiology and function. The skeletal muscle alcoholic myopathy is characterized by muscle weakness and difficulties in gait and locomotion, while chronic alcohol consumption ultimately leads to a decrease in cardiac contractility and output. In both tissues a loss of protein mass results in part from a decreased protein synthesis that initially manifests as a defect in translational efficiency. This review focuses on recent developments in understanding the cellular and molecular mechanisms by which alcohol impairs mRNA translation in skeletal and cardiac muscle, including identification of the signaling pathways and biochemical sites negatively impacted. Defective signaling potentially results from resistance to the normal stimulating effects of anabolic hormones (insulin and insulin-like growth factor-I) and nutrients (leucine) as well as increased production of several negative regulators of muscle mass. Overall, the biochemical mechanisms contributing to the pathogenesis of loss of skeletal and cardiac muscle are reviewed.