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

Abstract

of cyclooxygenase isoform activity and prostanoid production in normal and diseased Han:SPRD-cy rat kidneys. Am J Physiol Renal Physiol 290: F897-F904, 2006. First published October 18, 2005 doi:10.1152/ajprenal.00332.2005.-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 B 2 (TXB2, stable metabolite of TXA2), prostaglandin E2 (PGE2), and 6-keto-prostaglandin F1␣ (6-keto-PGF1␣, stable metabolite of PGI 2)] 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 Ϯ 0.02 vs. 0.45 Ϯ 0.11 ng prostanoids ⅐ min Ϫ1 ⅐ mg protein Ϫ1 (P Ͻ 0.001)] and COX-2 [0.64 Ϯ 0.10 vs. 2.32 Ϯ 0.22 ng prostanoids ⅐ min Ϫ1 ⅐ mg protein Ϫ1 (P Ͻ 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 ϳ2-10 times higher in diseased compared with normal kidneys. The differences between normal and diseased kidney prostanoids were in the order of TXB 2 Ͼ 6-keto-PGF 1␣ Ͼ PGE2, as determined by higher renal prostanoid levels and COX activity ratios of TXB 2/6-keto-PGF1␣, TXB2/PGE2, and 6-keto-PGF 1␣/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. thromboxane; prostaglandin CYCLOOXYGENASE (COX

Cyclooxygenase-2 Deficiency Enhances Th2 Immune Responses and Impairs Neutrophil Recruitment in Hepatic Ischemia/Reperfusion Injury

“…1). Indeed, it has been previously indicated that in COX KO mice, expression of the intact COX isoform is not up-regulated to compensate for the lack of the knocked-out isoform, suggesting that each isoform has a distinct role (34).…”

Prostaglandin E2mediates proliferation and chloride secretion in ADPKD cystic renal epithelia

“…Moreover, the PGE 2 concentration in renal tissue isolated from the Han:SPRD model of ADPKD is greater than that measured in littermate controls (35,44), suggesting that excessive autocrine production of PGE 2 may also contribute to the proliferative phenotype. To test whether PGE 2 concentrations are greater in PC-1-deficient cells, we measured PGE 2 in the conditioned media bathing the PC-1-deficient and PC-1-replete IMCD3 cells.…”

“…Recent observations suggest that altered prostanoid production contributes to these pathologic and clinical features. In kidneys of rodent PKD models and in renal cyst fluid from PKD patients, prostanoids, and more specifically PGE 2 , are present at higher concentrations than in controls (2,5,28,35,44). The molecular mechanisms by which mutations of cystogenic genes induce renal PGE 2 production remain unknown, but the levels of renal PGE 2 significantly affect the phenotype of PKD.…”

Distinctive effects of plant protein sources on renal disease progression and associated cardiac hypertrophy in experimental kidney disease

“…Western immunoblotting of proliferating cell nuclear antigen (PCNA) and chemokine receptor 2 (CCR2) was performed as described previously [38,39], with minor changes. Briefly, 30 mg of lyophilized kidney was homogenized in 100 volumes of ice-cold homogenization buffer containing protease inhibitors, centrifuged at 100 000 Â g for 30 min at 41C and the supernatant was removed.…”