Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.9.3.1 (cytochrome oxidase)
 8,822 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Type 2 diabetes has been related to a decrease of mitochondrial DNA (mtDNA) content. In this study, we show increased expression of the peroxisome proliferator-activated receptor-alpha (PPARalpha) and its target genes involved in fatty acid metabolism in skeletal muscle of Zucker Diabetic Fatty (ZDF) (fa/fa) rats. In contrast, the mRNA levels of genes involved in glucose transport and utilization (GLUT4 and phosphofructokinase) were decreased, whereas the expression of pyruvate dehydrogenase kinase 4 (PDK-4), which suppresses glucose oxidation, was increased. The shift from glucose to fatty acids as the source of energy in skeletal muscle of ZDF rats was accompanied by a reduction of subunit 1 of complex I (NADH dehydrogenase subunit 1, ND1) and subunit II of complex IV (cytochrome c oxidase II, COII), two genes of the electronic transport chain encoded by mtDNA. The transcript levels of PPARgamma Coactivator 1 (PGC-1) showed a significant reduction. Treatment with troglitazone (30 mg/kg/day) for 15 days reduced insulin values and reversed the increase in PDK-4 mRNA levels, suggesting improved insulin sensitivity. In addition, troglitazone treatment restored ND1 and PGC-1 expression in skeletal muscle. These results suggest that troglitazone may avoid mitochondrial metabolic derangement during the development of diabetes mellitus 2 in skeletal muscle.
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PMID:Impaired expression of NADH dehydrogenase subunit 1 and PPARgamma coactivator-1 in skeletal muscle of ZDF rats: restoration by troglitazone. 1456 25

We investigated whether chronic in vivo treatment with the peroxisome proliferator-activated receptor alpha agonist Wy-14,643 attenuates cardiac contractile function by impairing mitochondrial respiration. Wy-14,643 (25 mg kg(-1) day(-1)) was administered to Wistar rats by oral gavage for 14 consecutive days, after which ex vivo heart function, myocardial mitochondrial respiratory capacity, and metabolic gene expression were determined. Body and heart weights were not significantly altered following 14 days of Wy-14,643 administration. Heart perfusion studies showed significantly reduced systolic and developed pressures, while the rate pressure product declined by 36 +/- 2.6% (P < 0.01 vs. vehicle) after 14 days of Wy-14,643 treatment. State 3 mitochondrial respiration was lower in the Wy-14,643 group (P = 0.06 vs. vehicle). State 4 respiration and oligomycin-insensitive proton leak were significantly increased compared with matched controls. The rate of ADP phosphorylation was also decreased by 44.9 +/- 1.9% (P < 0.05 vs. vehicle). Pyruvate dehydrogenase kinase 4 (PDK4) and uncoupling protein 3 (UCP3) transcript levels were upregulated, while cytochrome oxidase II (COXII) expression was decreased following Wy-14,643 treatment. This study demonstrates that chronic in vivo Wy-14,643 administration impaired cardiac contractile function in parallel with decreased mitochondrial respiratory function and increased uncoupling.
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PMID:Chronic treatment with the peroxisome proliferator-activated receptor alpha agonist Wy-14,643 attenuates myocardial respiratory capacity and contractile function. 1936 Mar 80