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- W71392445 abstract "In response to reduced oxygen availability, important cellular and molecular adaptive changes occur in living organisms. Hypoxia-inducible factor (HIF) is a major adaptive mechanism and prolyl hydroxylase-binding domain proteins (PHD) is its most important negative regulator. However, peroxisome proliferator-activated receptor (PPARα), a nuclear transcription factor is activated in response to hypoxia/HIF-1α and regulates many of the downstream target genes. This study tested the hypothesis that inhibition of prolyl hydroxylase domain (PHD) would confer greater protection against ischemia by a mechanism involving PPARα activation. Rats were subjected to ischemia/reperfusion (I/R) for 48 hours with or without L-mimosine (L), a PHD inhibitor, fenofibrate, a PPARα ligand, MK886, a PPARα inhbitior. Renal blood flow (RBF; laser doppler flowmetry) recovered to 93±8%, 56±7% (p<0.001) and 87±10% (p<0.001) in control, ischemic and L-treated groups, respectively. Coincident with these changes, serum uric acid decreased by 41±6% (p<0.05) in I/R group versus 26±3% (p<0.05) following L- treatment. Compared to controls, serum nitric oxide decreased by 33±3% (p<0.05) in ischemic group while L treatment abolished the effect of ischemia (P<0.05). Similarly, 24hr urine volume increased by 100±13% (p < 0.001) in I/R and this was abolished by L (3%±0). 24-hour urinary protein excretion increased 5-fold in I/R group but was attenuated to a 2-fold increase in L-treated (p<0.05) group. Fenofibrate protected rats from the effects of I/R while MK886 blunted its effect. These findings suggest that stabilization of HIF-1α following inhibition of PHD protects against I/R in the rat kidney and that PPARα contributes to these effects." @default.
- W71392445 created "2016-06-24" @default.
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- W71392445 date "2013-04-01" @default.
- W71392445 modified "2023-09-26" @default.
- W71392445 title "Interactions of Hypoxia inducible factor (HIF)‐1α and Peroxisome proliferator‐activated receptor (PPAR) α in the protection against ischemia/reperfusion injury in the rat kidney" @default.
- W71392445 doi "https://doi.org/10.1096/fasebj.27.1_supplement.703.4" @default.
- W71392445 hasPublicationYear "2013" @default.
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