Etomoxir-induced PPARα-modulated enzymes protect during acute renal failure

被引:136
作者
Portilla, D
Dai, GH
Peters, JM
Gonzalez, FJ
Crew, MD
Proia, AD
机构
[1] Univ Arkansas Med Sci, Dept Internal Med, Div Nephrol, Little Rock, AR 72205 USA
[2] John L McClellan Mem Vet Adm Med Ctr, Little Rock, AR 72205 USA
[3] Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA
[4] NCI, Lab Metab, Bethesda, MD 20892 USA
[5] Univ Arkansas Med Sci, Dept Geriatr, Little Rock, AR 72205 USA
关键词
carnitine palmitoyltransferase; fatty acid oxidation; ischemia/reperfusion;
D O I
10.1152/ajprenal.2000.278.4.F667
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
Regulation of fatty acid beta-oxidation (FAO) represents an important mechanism for a sustained balance of energy production/utilization in kidney tissue. To examine the role of stimulated FAO during ischemia, Etomoxir (Eto), clofibrate, and WY-14,643 compounds were given 5 days prior to the induction of ischemia/reperfusion (I/R) injury. Compared with rats administered vehicle, Eto-, clofibrate-, and WY-treated rats had lower blood urea nitrogen and serum creatinines following I/R injury. Histological analysis confirmed a significant amelioration of acute tubular necrosis. YR injury led to a threefold reduction of mRNA and protein levels of acyl CoA oxidase (AOX) and cytochrome P4A1, as well as twofold inhibition of their enzymatic activities. Eto treatment prevented the reduction of mRNA and protein levels and the inhibition of the enzymatic activities of these two peroxisome proliferator-activated receptor-alpha (PPAR alpha) target genes during IIR injury. PPAR alpha null mice subjected to I/R injury demonstrated significantly enhanced cortical necrosis and worse kidney function compared with wild-type controls. These results suggest that upregulation of PPAR alpha-modulated FAO genes has an important role in the observed cytoprotection during I/R injury.
引用
收藏
页码:F667 / F675
页数:9
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