Submitted on April 1, 2005
Accepted on May 26, 2005
Functional coupling of adenine nucleotide translocase and mitochondrial creatine kinase is enhanced after exercise training in lung transplant skeletal muscle
Karen Guerrero1, Bernard Wuyam2, Paulette Mezin3, Isabelle Vivodtzev2, Marko Vendelin1, Jean-Christian Borel2, Rachid Hacini4, Olivier Chavanon4, Sandrine Imbeaud5, Valdur Saks1*, and Christophe Pison6
1 Laboratoire de Bioenergetique Fondamentale and Appliquee, INSERM - Universite Joseph Fourier, Grenoble, France
2 Laboratoire d'Exploration Fonctionnelle Cardio-Respiratoire, Centre Hospitalier Universitaire de Grenoble, Grenoble, France
3 Laboratoire de Pathologie Cellulaire, Centre Hospitalier Universitaire de Grenoble, Grenoble, France
4 Service de Chirurgie Cardiaque, Centre Hospitalier Universitaire de Grenoble, Grenoble, France
5 Genexpress, Genomique Fonctionnelle et Biologie des Systemes pour la Sante LGN, CNRS - Universite Pierre et Marie Curie, Paris, France
6 Laboratoire de Bioenergetique Fondamentale and Appliquee, INSERM - Universite Joseph Fourier, Grenoble, France; Departement de Medecine Aigue Specialisee, Centre Hospitalier Universitaire de Grenoble, Grenoble, France
* To whom correspondence should be addressed. E-mail: Valdur.Saks{at}ujf-grenoble.fr.
Mechanisms responsible for limitation of exercise capacity in lung transplant recipients (LR) and benefits gained by exercise training were studied. Mitochondrial respiration parameters, energy transfer and cell structure were assessed in Vastus lateralis biopsies using the permeabilized fiber technique with histochemical and morphometric measurements. Twelve male controls (C) and 12 LR performed exercise training over 12 weeks. Before exercise training, there were strong correlations between exercise capacity (VO2max and endurance time at 70% Pmax) and cellular events as assessed by percentage of type I fibers and apparent Km for exogenous ADP. Anti-calcineurins were not involved in LR exercise limitation since they were no differences in maximal mitochondrial rate of respiration (Vmax) before exercise training nor abnormalities in respiratory chain complexes as compared to C. Training resulted in a significant increase in physiological parameters both at cellular (apparent Km for exogenous ADP and stimulating effect of creatine) and integrated levels (V02max, Pventilatory threshold, Pmax, endurance time at 70% Pmax) in LR and C. After training, improvements in V02max and in Vmax were noted as well as changes in endurance time and percent of type I fibers. Since there were no changes in diameters and fiber types, baseline alteration of apparent Km for exogenous ADP and its improvement after training might be related to changes within the Intracellular Energetic Units (ICEUs). After training, ICEUs exhibited a higher control of mitochondrial respiration by creatine linked to a more efficient functional coupling ANT-MtCK resulting in better exercise performances in C and LR.
