Selectivity of cyclooxygenase isoform activity and prostanoid production in normal and diseased Han:SPRD-cyrat kidneys

American Journal of Physiology - Renal Physiology - Tập 290 Số 4 - Trang F897-F904 - 2006
Lori Warford‐Woolgar1, Claudia Yu-Chen Peng, Jamie N. Shuhyta, Andrew Wakefield, Deepa Sankaran, Malcolm R. Ogborn, Harold M. Aukema
1Department of Human Nutritional Sciences, University of Manitoba, Winnipeg, Canada

Tóm tắt

Renal prostanoids are important regulators of normal renal function and maintenance of renal homeostasis. In diseased kidneys, renal cylooxygenase (COX) expression and prostanoid formation are altered. With the use of the Han:Sprague-Dawley- cy rat, the aim of this study was to determine the relative contribution of renal COX isoforms (protein, gene expression, and activity) on renal prostanoid production [thromboxane B2(TXB2, stable metabolite of TXA2), prostaglandin E2(PGE2), and 6-keto-prostaglandin F1α(6-keto-PGF1α, stable metabolite of PGI2)] in normal and diseased kidneys. In diseased kidneys, COX-1-immunoreactive protein and mRNA levels were higher and COX-2 levels were lower compared with normal kidneys. In contrast, COX activities were higher in diseased compared with normal kidneys for both COX-1 [0.05 ± 0.02 vs. 0.45 ± 0.11 ng prostanoids·min−1·mg protein−1( P < 0.001)] and COX-2 [0.64 ± 0.10 vs. 2.32 ± 0.22 ng prostanoids·min−1·mg protein−1( P < 0.001)]. As the relative difference in activity was greater for COX-1, the ratio of COX-1/COX-2 was higher in diseased compared with normal kidneys, although the predominant activity was still due to the COX-2 isoform in both genotypes. Endogenous and steady-state in vitro levels of prostanoids were ∼2–10 times higher in diseased compared with normal kidneys. The differences between normal and diseased kidney prostanoids were in the order of TXB2> 6-keto-PGF1α> PGE2, as determined by higher renal prostanoid levels and COX activity ratios of TXB2/6-keto-PGF1α, TXB2/PGE2, and 6-keto-PGF1α/PGE2. This specificity in both the COX isoform type and for the prostanoids produced has implications for normal and diseased kidneys in treatments involving selective inhibition of COX isoforms.

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American Journal of Physiology - Renal Physiology

Tập 290 Số 4

F897-F904

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