{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T14:56:15Z","timestamp":1790866575906,"version":"4.1.0"},"reference-count":49,"publisher":"American Physiological Society","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Renal Physiology"],"published-print":{"date-parts":[[2006,6]]},"abstract":"<jats:p>To examine the interaction of nitric oxide (NO) and cyclooxygenase (COX-2) and the signaling pathway involved, primary cultured rabbit cortical thick ascending limb (cTAL) were used. In these cells, immunoreactive COX-2 and vasodilatory prostaglandins were increased by a NO donor, S-nitros- N-acetylpenicillamine (SNAP; 2.5 \u00b1 0.3-fold control, n = 6, P &lt; 0.01). SNAP increased expression of phosphorylated p38 (pp38; 2.4 \u00b1 0.3-fold control; n = 5; P &lt; 0.01), which was inhibited by the p38 inhibitor SB-203580 (1.3 \u00b1 0.1-fold control, n = 5, P &lt; 0.01). SB-203580 inhibited SNAP-induced COX-2 expression [1.4 \u00b1 0.2-fold control, n = 6, not significant (NS) vs. control] and levels of PGE<jats:sub>2<\/jats:sub>significantly. In cTAL cells transfected with a luciferase reporter driven by the wild-type mouse COX-2 promoter, SNAP stimulated luciferase activity, which was reversed by SB-203580 (control vs. SNAP vs. SNAP + SB-203580: 1.4 \u00b1 0.2-, 8.3 \u00b1 1.4-, and 0.4 \u00b1 0.1-fold control, respectively, n = 4, P &lt; 0.01). Electrophoretic mobility shift assay indicated that SNAP stimulated nuclear factor (NF)-\u03baB binding activity in cTAL that was also inhibited by the p38 inhibitor. SNAP was not able to stimulate a mutant COX-2 promoter construct that is not activated by NF-\u03baB (0.9 \u00b1 0.1, 1.2 \u00b1 0.1, and 1.0 \u00b1 0.2 respectively, n = 4, NS). Low chloride increased COX-2 expression (2.7 \u00b1 0.4-fold control, n = 6, P &lt; 0.01) and pp38 expression (2.8 \u00b1 0.3-fold; n = 5, P &lt; 0.01), which were reversed by the specific NO synthase (NOS) inhibitor 7-nitroindazole. Administration of a low-salt diet increased immunoreactive COX-2 and neuronal NOS (nNOS) in the macula densa and surrounding cTAL of kidneys of wild-type mice but did not significantly elevate COX-2 expression in nNOS<jats:sup>\u2212\/\u2212<\/jats:sup>mice. In summary, these studies indicate that, in cTAL, NO can increase COX-2 expression in cTAL and macula densa through p38-dependent signaling pathways via activation of NF-\u03baB.<\/jats:p>","DOI":"10.1152\/ajprenal.00315.2005","type":"journal-article","created":{"date-parts":[[2005,12,28]],"date-time":"2005-12-28T01:23:48Z","timestamp":1135733028000},"page":"F1391-F1397","source":"Crossref","is-referenced-by-count":26,"title":["Nitric oxide stimulates cyclooxygenase-2 in cultured cTAL cells through a p38-dependent pathway"],"prefix":"10.1152","volume":"290","author":[{"given":"Hui-Fang","family":"Cheng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming-Zhi","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raymond 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