부산대학교 도서관

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.bbrc.2007.10.062 Byline: Adam J. Belanger, Zhengyu Luo, Karen A. Vincent, Geoffrey Y. Akita, Seng H. Cheng, Richard J. Gregory, Canwen Jiang Keywords: Hypoxia; HIF-1; PPAR[alpha]; M-CPT I; Neural lipid accumulation Abstract: In response to cellular hypoxia, cardiomyocytes adapt to consume less oxygen by shifting ATP production from mitochondrial fatty acid [beta]-oxidation to glycolysis. The transcriptional activation of glucose transporters and glycolytic enzymes by hypoxia is mediated by hypoxia-inducible factor 1 (HIF-1). In this study, we examined whether HIF-1 was involved in the suppression of mitochondrial fatty acid [beta]-oxidation in hypoxic cardiomyocytes. We showed that either hypoxia or adenovirus-mediated expression of a constitutively stable hybrid form (HIF-1[alpha]/VP16) suppressed mitochondrial fatty acid metabolism, as indicated by an accumulation of intracellular neutral lipid. Both treatments also reduced the mRNA levels of muscle carnitine palmitoyltransferase I which catalyzes the rate-limiting step in the mitochondrial import of fatty acids for [beta]-oxidation. Furthermore, adenovirus-mediated expression of HIF-1[alpha]/VP16 in cardiomyocytes under normoxic conditions also mimicked the reduction in the DNA binding activity of peroxisome proliferator-activated receptor [alpha] (PPAR[alpha])/retinoid X receptor (RXR), in the presence or absence of a PPAR[alpha] ligand. These results suggest that HIF-1 may be involved in hypoxia-induced suppression of fatty acid metabolism in cardiomyocytes by reducing the DNA binding activity of PPAR[alpha]/RXR. Author Affiliation: Genzyme Corporation, 49 New York Avenue, Framingham, MA 01701, USA Article History: Received 2 October 2007