Altered mitochondrial apparent affinity for ADP and impaired function of mitochondrial creatine kinase in gluteus medius of patients with hip osteoarthritis

• Published in: American journal of physiology. Regulatory, integrative and comparative physiology integrative and comparative physiology, 2006-05, Vol.290 (5), p.R1271-R1275
• Main Authors: Eimre, Margus, Puhke, Raivo, Alev, Karin, Seppet, Evelin, Sikkut, Anneli, Peet, Nadezhda, Kadaja, Lumme, Lenzner, Aleks, Haviko, Tiit, Seene, Teet, Saks, Valdur A, Seppet, Enn K
• Format: Article
• Language: English
• Subjects: Adenosine Diphosphate; Adenosine Diphosphate - metabolism; Aged; Biochemistry, Molecular Biology; Creatine Kinase; Creatine Kinase - metabolism; Energy Metabolism; Energy Metabolism - drug effects; Female; Humans; Life Sciences; Male; Middle Aged; Mitochondria; Mitochondria - enzymology; Mitochondria - metabolism; Muscle, Smooth; Muscle, Smooth - drug effects; Myosin Heavy Chains; Myosin Heavy Chains - metabolism; Osteoarthritis, Hip; Osteoarthritis, Hip - enzymology; Osteoarthritis, Hip - metabolism; Oxidative Phosphorylation; Oxidative Phosphorylation - drug effects
• ISSN: 0363-6119; 1522-1490
• DOI: 10.1152/ajpregu.00651.2005

1 Department of Pathophysiology, Centre of Molecular and Clinical Medicine, Faculty of Medicine, 2 Department of Functional Morphology, Faculty of Exercise and Sport Science, 3 Department of Traumatology and Orthopaedics, Faculty of Medicine, University of Tartu, Tartu, Estonia; 4 Laboratory of Bioenergetics, National Institute of Chemical Physics and Biophysics, Tallinn, Estonia; and 5 Laboratory of Bioenergetics, Joseph Fourier University, Grenoble, France Submitted 6 September 2005 ; accepted in final form 9 December 2005 The cellular energy metabolism in human musculus gluteus medius (MGM) under normal conditions and hip osteoarthritis (OA) was explored. The functions of oxidative phosphorylation and energy transport systems were analyzed in permeabilized (skinned) muscle fibers by oxygraphy, in relation to myosin heavy chain (MHC) isoform distribution profile analyzed by SDS-PAGE, and to creatine kinase (CK) and adenylate kinase (AK) activities measured spectrophotometrically in the intact muscle. The results revealed high apparent K m for ADP in regulation of respiration that decreased after addition of creatine in MGM of traumatic patients (controls). OA was associated with increased sensitivity of mitochondrial respiration to ADP, decreased total activities of AK and CK with major reduction in mi-CK fraction, and attenuated effect of creatine on apparent K m for ADP compared with control group. It also included a complete loss of type II fibers in a subgroup of patients with the severest disease grade. It is concluded that energy metabolism in MGM cells is organized into functional complexes of mitochondria and ATPases. It is suggested that because of degenerative remodeling occurring during development of OA, these complexes become structurally and functionally impaired, which results in increased access of exogenous ADP to mitochondria and dysfunction of CK-phosphotransfer system. musculus gluteus medius ; myosin heavy chains; mitochondrial respiration; energy transfer Address for reprint requests and other correspondence: E. K. Seppet, Dept. of Pathophysiology, Faculty of Medicine, Univ. of Tartu, 19 Ravila St., 50411 Tartu, Estonia (E-mail: enn.seppet{at}ut.ee )