Altered mitochondrial apparent affinity for ADP and impaired function of mitochondrial creatine kinase in gluteus medius of patients with hip osteoarthritis.
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 Km 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 Km 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.
Eimre
Margus
M
Dept. of Pathophysiology, Centre of Molecular and Clinical Medicine, Faculty of Medicine, Univ. of Tartu, 19 Ravila St., 50411 Tartu, Estonia.
Puhke
Raivo
R
Alev
Karin
K
Seppet
Evelin
E
Sikkut
Anneli
A
Peet
Nadezhda
N
Kadaja
Lumme
L
Lenzner
Aleks
A
Haviko
Tiit
T
Seene
Teet
T
Saks
Valdur A
VA
Seppet
Enn K
EK
D000244:Adenosine Diphosphate / Q000378:metabolism*; D000368:Aged; D003402:Creatine Kinase / Q000378:metabolism*; D004734:Energy Metabolism / Q000187:drug effects; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000201:enzymology / Q000378:metabolism*; D009130:Muscle, Smooth / Q000187:drug effects*; D018995:Myosin Heavy Chains / Q000378:metabolism; D015207:Osteoarthritis, Hip / Q000201:enzymology / Q000378:metabolism*; D010085:Oxidative Phosphorylation / Q000187:drug effects
D000244:Adenosine Diphosphate; D003402:Creatine Kinase; D018995:Myosin Heavy Chains