Altered gene expression of uncoupling protein-2 and -3 in stroke-prone spontaneously hypertensive rats.

Abstract

Uncoupling proteins (UCPs) are the inner mitochondrial membrane-associated proteins, which dissipate the proton gradient and generate heat instead of ATP. The involvement of UCPs in energy expenditure and glucose metabolism has been suggested. Recently, we succeeded in cloning of rat UCP2 and UCP3. The aim of this study was to elucidate the pathophysiological role of UCP2 and UCP3 in hypertension associated with hyperglycemia in stroke-prone spontaneously hypertensive rats (SHR-SP). UCP2 and UCP3 mRNA levels of cardiac and gastrocnemius muscles in SHR-SP and Wistar-Kyoto (WKY) rats were determined at 6 weeks (prehypertensive stage) and at 15 weeks (hypertensive stage). UCP2 and UCP3 mRNA levels in the heart of SHR-SP at 6 weeks were significantly higher than those of WKY rats (1.6-fold, 3.6-fold, respectively). These tendencies did not change in the heart at 15 weeks. UCP2 and UCP3 mRNA levels in the skeletal muscle of SHR-SP at 6 weeks were significantly higher than those of WKY rats (1.4-fold, 2.4-fold, respectively). In contrast, at 15 weeks, UCP2 and UCP3 mRNA levels in the skeletal muscle of SHR-SP were significantly lower than those of WKY rats (70 and 36% of WKY rats, respectively). Therefore, the decrease of UCP2 and UCP3 in the skeletal muscle was observed with the concomitant development of hypertension in SHR-SP. UCP2 mRNA levels in the epididymal fat of SHR-SP at 15 weeks were similar to that of WKY rats. Altered gene expression of UCP2 and UCP3 might be related to some pathophysiological aspects in hypertension and glucose metabolism in SHR-SP.