{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T02:48:08Z","timestamp":1761101288746,"version":"3.41.0"},"reference-count":51,"publisher":"American Physiological Society","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Gastrointestinal and Liver Physiology"],"published-print":{"date-parts":[[2002,3,1]]},"abstract":"<jats:p>The nitric oxide (NO) synthase inhibitor N<jats:sup>\u03c9<\/jats:sup>-nitro-l-arginine (l-NNA) inhibits heat stress (HS)-induced NO production and the inducible 70-kDa heat shock protein (HSP-70i) in many rodent organs. We used human intestinal epithelial T84 cells to characterize the inhibitory effect of l-NNA on HS-induced HSP-70i expression. Intracellular Ca<jats:sup>2+<\/jats:sup>concentration ([Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>) was measured using fura-2, and protein kinase C (PKC), and PKA activities were determined. HS increased HSP-70i mRNA and protein in T84 cells exposed to 45\u00b0C for 10 min and allowed to recover for 6 h. l-NNA treatment for 1 h before HS inhibited the induction of HSP-70i mRNA and protein, with an IC<jats:sub>50<\/jats:sub>of 0.0471 \u00b1 0.0007 \u03bcM. Because the HS-induced increase in HSP-70i mRNA and protein is Ca<jats:sup>2+<\/jats:sup>dependent, we measured [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>after treating cells withl-NNA. l-NNA at 100 \u03bcM significantly decreased resting [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>. Likewise, treatment with 1 \u03bcM GF-109203X or H-89 (inhibitors of PKC and PKA, respectively) for 30 min also significantly decreased [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>and inhibited HS-induced increase in HSP-70i. GF-109203X- or H-89-treated cells failed to respond tol-NNA by further decreasing [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>and HSP-70i. l-NNA effectively blocked heat shock factor-1 (HSF1) translocation from the cytosol to the nucleus, a process requiring PKC phosphorylation. These results suggest that l-NNA inhibits HSP-70i by reducing [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>and decreasing PKC and PKA activity, thereby blocking HSF1 translocation from the cytosol to the nucleus.<\/jats:p>","DOI":"10.1152\/ajpgi.00138.2001","type":"journal-article","created":{"date-parts":[[2015,3,3]],"date-time":"2015-03-03T19:55:14Z","timestamp":1425412514000},"page":"G415-G423","source":"Crossref","is-referenced-by-count":11,"title":["<i>N<\/i><sup>\u03c9<\/sup>-nitro-<scp>l<\/scp>-arginine inhibits inducible HSP-70 via Ca<sup>2+<\/sup>, PKC, and PKA in human intestinal epithelial T84 cells"],"prefix":"10.1152","volume":"282","author":[{"given":"Juliann G.","family":"Kiang","sequence":"first","affiliation":[{"name":"Department of Cellular Injury, Walter Reed Army Institute of Research, Silver Spring 20910-7500; and Departments of"},{"name":"Medicine and"},{"name":"Pharmacology, Uniformed Services University of the Health Sciences, Bethesda, Maryland 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