galactose enhances oxidative metabolism and reveals mitochondrial dysfunction in human primary muscle cells半乳糖提高氧化代谢和揭示人类主要肌肉细胞线粒体功能障碍.pdfVIP

Galactose Enhances Oxidative Metabolism and Reveals Mitochondrial Dysfunction in Human Primary Muscle Cells ´ 1 1 1 1 2 Celine Aguer , Daniela Gambarotta , Ryan J. Mailloux , Cynthia Moffat , Robert Dent , Ruth 3 1 McPherson , Mary-Ellen Harper * 1 Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ontario, Canada, 2 Ottawa Hospital Weight Management Clinic, Ottawa, Ontario, Canada, 3 Division of Cardiology, University of Ottawa Heart Institute, Ottawa, Ontario, Canada Abstract Background: Human primary myotubes are highly glycolytic when cultured in high glucose medium rendering it difficult to study mitochondrial dysfunction. Galactose is known to enhance mitochondrial metabolism and could be an excellent model to study mitochondrial dysfunction in human primary myotubes. The aim of the present study was to 1) characterize the effect of differentiating healthy human myoblasts in galactose on oxidative metabolism and 2) determine whether galactose can pinpoint a mitochondrial malfunction in post-diabetic myotubes. Methodology/Principal Findings: Oxygen consumption rate (OCR), lactate levels, mitochondrial content, citrate synthase and cytochrome C oxidase activities, and AMPK phosphorylation were determined in healthy myotubes differentiated in different sources/concentrations of carbohydrates: 25 mM glucose (high glucose (HG)), 5 mM glucose (low glucose (LG)) or 10 mM galactose (GAL). Effect of carbohydrates on OCR was also determined in myotubes derived from post-diabetic patients and matched obese non-diabetic subjects. OCR was significantly increased whereas anaerobic glycolysis was significantly decreased