INCREASED EXPRESSION OF PGC-1 MESSENGER RNA IN RAT SKELETAL MUSCLE EXPOSED TO AICAR IN VITRO

Abstract

Exercise increases oxidative enzymes proteins in mitochondria of skeletal muscle. However, its exact mechanisms are not known. Recently, we found that exercise training increases mRNA of peroxisome proliferator-activated receptor âÁ coactivator-1 (PGC-1) in rat skeletal muscle (Goto et al. Biochem. Biophys. Res. Commun. 274:350–354, 2000). Since PGC-1 is a transcription co-activator that has been postulated to be a key factor for biogenesis of mitochondria proteins induced by several physiological stimuli, we are hypothesizing PGC-1 may be involved in mechanism related to enhanced mitochondria protein expression after exercise training. Regarding to the mechanisms of enhanced mitochondria protein expression in relation to exercise, Winder et al. (J. Appl. Physiol. 88:2219–2226, 2000) reported that expression of mitochondria enzyme protein is enhanced by AICAR (5üf-amino-4-imidazolecarboxamide ribonucleoside), a compound that activates AMP-activated protein kinase (AMPK) activity, an enzyme known to be stimulated during exercise. Therefore, we observed effects of AICAR on PGC-1 mRNA expression on skeletal muscle. Epitrochlearis muscles from male Sprague-Dawley rats with a body weight approximately 110 g were excised and incubated for 18 hours in oxygenated culture medium with or without 0.5 mM AICAR. After AICAR incubation, PGC-1 mRNA increased to the level 1.9 times higher than that observed in the control muscle (n = 6, p < 0.001). This result may suggest that, during exercise, AMPK enhances expression of PGC-1 that, possibly later, induces biogenesis of some mitochondria proteins.