Induction of cyclooxygenase-2 in thick ascending limb cells by adrenalectomy

• Published in: Journal of the American Society of Nephrology 2001-04, Vol.12 (4), p.649-658
• Main Authors: VIO, Carlos P, AN, Shao-Jian, CESPEDES, Carlos, MCGIFF, John C, FERRERI, Nicholas R
• Format: Article
• Language: English
• Subjects: Adrenalectomy; Animals; Biological and medical sciences; Cyclooxygenase 2; Dexamethasone - pharmacology; Enzyme Induction - physiology; Glucocorticoids - pharmacology; Isoenzymes - antagonists & inhibitors; Isoenzymes - genetics; Isoenzymes - metabolism; Kidney - cytology; Kidney - enzymology; Loop of Henle - cytology; Loop of Henle - enzymology; Macrophages - enzymology; Male; Medical sciences; Postoperative Period; Prostaglandin-Endoperoxide Synthases - genetics; Prostaglandin-Endoperoxide Synthases - metabolism; Rats; Rats, Sprague-Dawley; RNA, Messenger - metabolism; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Surgery of endocrine glands
• ISSN: 1046-6673; 1533-3450
• DOI: 10.1681/ASN.V124649

Adrenalectomized (ADX) and sham-operated rats received either dexamethasone (DEX) or vehicle. Renal tissue was used for morphologic analysis, assessment of cyclooxygenase-2 (COX-2) protein expression and mRNA accumulation, and quantitation of COX-2 activity. In untreated or shamoperated rats, COX-2 protein was observed in a subset of tubular epithelial cells (30% of TAL cells expressed COX-2 in a manner consistent with recruitment of COX-2-positive TAL cells toward the medulla. Treatment of ADX rats with DEX reduced the number of COX-2-positive cells to that observed in sham-operated or intact rats. COX-2 mRNA accumulation was increased by ADX and partially attenuated by treatment with DEX. Western blot analysis of cortical microsomes revealed a substantial increase in COX-2 expression in ADX rats, compared with ADX/DEX-treated, sham-operated, or intact rats. The increase in COX-2 protein expression was associated with a twofold increase in prostaglandin E(2) formation by cortical microsomes obtained from ADX rats, compared with sham-operated rats. It is concluded that ADX induces expression of enzymatically active COX-2, such that expression occurs in the cortical TAL and proceeds in a defined pattern toward the outer medullary TAL. It is suggested that ADX induces expression of TAL cells that, in the basal state, do not express COX-2 protein.