Submitted on September 6, 2005
Accepted on December 9, 2005
Altered mitochondrial apparent affinity for ADP and impaired function of mitochondrial creatine kinase in gluteus medius of patients with hip osteoarthritis
Margus Eimre1, Raivo Puhke2, Karin Alev2, Evelin Seppet1, Anneli Sikkut2, Nadezhda Peet1, Lumme Kadaja1, Aleks Lenzner3, Tiit Haviko3, Teet Seene2, Valdur A Saks4, and Enn K Seppet1*
1 Department of Pathophysiology, Centre of Molecular and Clinical Medicine, University of Tartu, Tartu, Estonia
2 Department of Functional Morphology, University of Tartu, Tartu, Estonia
3 Department of Traumatology and Orthopaedics, University of Tartu, Tartu, Estonia
4 Laboratory of Bioenergetics, National Institute of Chemical Physics and Biophysics, Tallinn, Estonia; Laboratory of Bioenergetics, Joseph Fourier University, Grenoble, France
* To whom correspondence should be addressed. E-mail: enn.seppet{at}ut.ee.
The cellular energy metabolism in human m. 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 analysed 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 to 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 due to degenerative remodeling occurring during development of OA these complexes become structurally and functionally impaired that results in increased access of exogenous ADP to mitochondria and dysfunction of CK-phosphotransfer system.
