{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T15:26:09Z","timestamp":1781105169223,"version":"3.54.1"},"reference-count":48,"publisher":"National Academy of Sciences","issue":"26","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2000,12,19]]},"abstract":"<jats:p>\n                    NO, produced from\n                    <jats:sc>l<\/jats:sc>\n                    -arginine in a reaction catalyzed by NO synthase, is an endogenous free radical with multiple functions in mammalian cells. Here, we demonstrate that endogenously produced NO can suppress c-Jun N-terminal kinase (JNK) activation in intact cells. Treatment of BV-2 murine microglial cells with IFN-\u03b3 induced endogenous NO production, concomitantly suppressing JNK1 activation. Similarly, IFN-\u03b3 induced suppression of JNK1 activation in RAW264.7 murine macrophage cells and rat alveolar macrophages. The IFN-\u03b3-induced suppression of JNK1 activation in BV-2, RAW264.7, or rat alveolar macrophage cells was completely prevented by\n                    <jats:italic>N<\/jats:italic>\n                    <jats:sup>G<\/jats:sup>\n                    -nitro-\n                    <jats:sc>l<\/jats:sc>\n                    -arginine, a NO synthase inhibitor. Interestingly, the IFN-\u03b3-induced suppression of JNK1 activation was not affected by 1\n                    <jats:italic>H<\/jats:italic>\n                    -[1,2,4]oxadiazolo[4,3-\n                    <jats:italic>a<\/jats:italic>\n                    ]quinoxalin-1-one, an inhibitor of guanylyl cyclase. 8-Bromo-cGMP, a membrane-permeant analogue of cGMP, did not change JNK1 activation in intact cells either. In contrast,\n                    <jats:italic>S<\/jats:italic>\n                    -nitro-\n                    <jats:italic>N<\/jats:italic>\n                    -acetyl-\n                    <jats:sc>dl<\/jats:sc>\n                    -penicillamine (SNAP), a NO donor, inhibited JNK1 activity\n                    <jats:italic>in vitro<\/jats:italic>\n                    . Furthermore, a thiol reducing agent, DTT, reversed not only the\n                    <jats:italic>in vitro<\/jats:italic>\n                    inhibition of JNK1 activity by SNAP but also the\n                    <jats:italic>in vivo<\/jats:italic>\n                    suppression of JNK1 activity by IFN-\u03b3. Substitution of serine for cysteine-116 in JNK1 abolished the inhibitory effect of IFN-\u03b3 or SNAP on JNK1 activity\n                    <jats:italic>in vivo<\/jats:italic>\n                    or\n                    <jats:italic>in vitro<\/jats:italic>\n                    , respectively. Moreover, IFN-\u03b3 enhanced endogenous\n                    <jats:italic>S<\/jats:italic>\n                    -nitrosylation of JNK1 in RAW264.7 cells. Collectively, our data suggest that endogenous NO mediates the IFN-\u03b3-induced suppression of JNK1 activation in macrophage cells by means of a thiol-redox mechanism.\n                  <\/jats:p>","DOI":"10.1073\/pnas.97.26.14382","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:44:19Z","timestamp":1027680259000},"page":"14382-14387","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":209,"title":["Nitric oxide negatively regulates c-Jun N-terminal kinase\/stress-activated protein kinase by means of\n                    <i>S<\/i>\n                    -nitrosylation"],"prefix":"10.1073","volume":"97","author":[{"given":"Hee-Sae","family":"Park","sequence":"first","affiliation":[{"name":"National Creative Research Initiative Center for Cell Death, Graduate School of Biotechnology, Korea University, Seoul, 136-701, Korea; and Department of Physiology, School of Medicine, Ajou University, Suwon 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