title: Hypoxia-induced decrease of UCP3 gene expression in rat heart parallels metabolic gene switching but fails to affect mitochondrial respiratory coupling.
abstract: Mitochondrial uncoupling proteins 2 and 3 (UCP2 and UCP3) are postulated to contribute to antioxidant defense, nutrient partitioning, and energy efficiency in the heart. To distinguish isotype function in response to metabolic stress we measured cardiac mitochondrial function and cardiac UCP gene expression following chronic hypobaric hypoxia. Isolated mitochondrial O(2) consumption and ATP synthesis rate were reduced but respiratory coupling was unchanged compared to normoxic groups. Concurrently, left ventricular UCP3 mRNA levels were significantly decreased with hypoxia (p<0.05) while UCP2 levels remained unchanged versus controls. Diminished UCP3 expression was associated with coordinate regulation of counter-regulatory metabolic genes. From these data, we propose a role for UCP3 in the regulation of fatty acid oxidation in the heart as opposed to uncoupling of mitochondria. Moreover, the divergent hypoxia-induced regulation of UCP2 and UCP3 supports distinct mitochondrial regulatory functions of these inner mitochondrial membrane proteins in the heart in response to metabolic stress.
authors.affiliation: Hatter Institute for Cardiology Research, University of Cape Town Faculty of Health Sciences, 7925 Observatory, South Africa. mfessop@capeheart.uct.ac.za
authors.forename: M Faadiel
authors.initials: MF
authors.lastname: Essop
authors.forename: Peter
authors.initials: P
authors.lastname: Razeghi
authors.forename: Chris
authors.initials: C
authors.lastname: McLeod
authors.forename: Martin E
authors.initials: ME
authors.lastname: Young
authors.forename: Heinrich
authors.initials: H
authors.lastname: Taegtmeyer
authors.forename: Michael N
authors.initials: MN
authors.lastname: Sack
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000737:chemistry; D002352:Carrier Proteins / Q000096:biosynthesis*; D005227:Fatty Acids / Q000378:metabolism; D005786:Gene Expression Regulation; D000860:Hypoxia; D007473:Ion Channels; D050356:Lipid Metabolism; D026901:Membrane Transport Proteins / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism; D010101:Oxygen Consumption; D011522:Protons; D012313:RNA / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000071246:Uncoupling Protein 2; D000071247:Uncoupling Protein 3
chemical_list: D000975:Antioxidants; D002352:Carrier Proteins; D005227:Fatty Acids; D007473:Ion Channels; D026901:Membrane Transport Proteins; D024101:Mitochondrial Proteins; D011522:Protons; D012333:RNA, Messenger; C000604391:Ucp2 protein, rat; C000604394:Ucp3 protein, rat; D000071246:Uncoupling Protein 2; D000071247:Uncoupling Protein 3; D012313:RNA; D010100:Oxygen