TY - JOUR
T1 - Changes in uncoupling protein-2 and -3 expression in aging rat skeletal muscle, liver, and heart
AU - Barazzoni, Rocco
AU - Nair, K. Sreekumaran
PY - 2001/3
Y1 - 2001/3
N2 - Uncoupling protein (UCP)-2 and -3 mediate mitochondrial (mt) proton leak in vitro and are potential regulators of energy expenditure and ATP production. Aging is associated with alteration of tissue functions, suggesting impaired mtATP production. To determine whether age-related changes in UCP expression occur, we measured the transcript levels of UCP-2 and -3 in skeletal muscle, liver, and heart in 6- and 27-mo-old rats. UCP-2 transcripts were higher in old animals in the white (+100%) and red (+70%, both P < 0.04) gastrocnemius muscle and in the liver (+300%, P < 0.03), whereas they were comparable in the heart in both age groups. UCP-2 transcript levels correlated positively with mitochondrial-encoded cytochrome c oxidase transcripts normalized for mtDNA (P < 0.01) and negatively with mtDNA copy number (P < 0.001). UCP-3 transcripts were lower in the less oxidative white (-50%, P < 0.04) and unchanged in the more oxidative red (-15%, P = 0.41) gastrocnemius muscle in old animals. Similar changes at protein level were confirmed by UCP-2 protein in aging liver (+300%, P < 0.01) and UCP-2 (+85%, P < 0.05) and UCP-3 (-30%, P = 0.4) protein in aging mixed gastrocnemius muscle. Aging is thus associated with tissue-specific changes of UCP-2 and -3 gene expression. Increased UCP-2 expression may limit ATP production and is related to mitochondrial gene expression in aging muscles and liver. Different age-related changes may reflect differential regulation of UCP-2 and -3 in skeletal muscle. The current data suggest a potential role of uncoupling proteins to alter energy production in aging tissues.
AB - Uncoupling protein (UCP)-2 and -3 mediate mitochondrial (mt) proton leak in vitro and are potential regulators of energy expenditure and ATP production. Aging is associated with alteration of tissue functions, suggesting impaired mtATP production. To determine whether age-related changes in UCP expression occur, we measured the transcript levels of UCP-2 and -3 in skeletal muscle, liver, and heart in 6- and 27-mo-old rats. UCP-2 transcripts were higher in old animals in the white (+100%) and red (+70%, both P < 0.04) gastrocnemius muscle and in the liver (+300%, P < 0.03), whereas they were comparable in the heart in both age groups. UCP-2 transcript levels correlated positively with mitochondrial-encoded cytochrome c oxidase transcripts normalized for mtDNA (P < 0.01) and negatively with mtDNA copy number (P < 0.001). UCP-3 transcripts were lower in the less oxidative white (-50%, P < 0.04) and unchanged in the more oxidative red (-15%, P = 0.41) gastrocnemius muscle in old animals. Similar changes at protein level were confirmed by UCP-2 protein in aging liver (+300%, P < 0.01) and UCP-2 (+85%, P < 0.05) and UCP-3 (-30%, P = 0.4) protein in aging mixed gastrocnemius muscle. Aging is thus associated with tissue-specific changes of UCP-2 and -3 gene expression. Increased UCP-2 expression may limit ATP production and is related to mitochondrial gene expression in aging muscles and liver. Different age-related changes may reflect differential regulation of UCP-2 and -3 in skeletal muscle. The current data suggest a potential role of uncoupling proteins to alter energy production in aging tissues.
KW - Adenosine 5′-triphosphate
KW - Energy metabolism
KW - Mitochondria
KW - Proton leak
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U2 - 10.1152/ajpendo.2001.280.3.e413
DO - 10.1152/ajpendo.2001.280.3.e413
M3 - Article
C2 - 11171595
AN - SCOPUS:0035000177
SN - 0193-1849
VL - 280
SP - E413-E419
JO - American Journal of Physiology - Endocrinology and Metabolism
JF - American Journal of Physiology - Endocrinology and Metabolism
IS - 3 43-3
ER -