{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T01:37:01Z","timestamp":1773279421472,"version":"3.50.1"},"reference-count":50,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2003,6,1]],"date-time":"2003-06-01T00:00:00Z","timestamp":1054425600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004084","name":"Korea Science and Engineering Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004084","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2003,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Nitric oxide (NO) functions not only as an important signaling molecule in the brain by producing cGMP, but also regulates neuronal cell apoptosis. The mechanism by which NO regulates apoptosis is unclear. In this study, we demonstrated that NO, produced either from the NO donor\n                    <jats:italic>S<\/jats:italic>\n                    \u2010nitroso\u2010N\u2010acetyl\u2010\n                    <jats:sc>D,L<\/jats:sc>\n                    \u2010penicillamine (SNAP) or by transfection of neuronal NO synthase, suppressed 6\u2010hydroxydopamine (6\u2010OHDA)\u2010induced apoptosis in PC12 cells by inhibiting mitochondrial cytochrome c release, caspase\u20103 and \u20109 activation, and DNA fragmentation. This protection was significantly reversed by the soluble guanylyl cyclase inhibitor 1H\u2010(1,2,4)\u2010oxadiazole[4,3\u2010a]quinoxalon\u20101\u2010one, indicating that cGMP is a key mediator in NO\u2010mediated anti\u2010apoptosis. Moreover, the membrane\u2010permeable cGMP analog 8\u2010Br\u2010cGMP inhibited 6\u2010OHDA\u2010induced apoptosis. These anti\u2010apoptotic effects of SNAP and 8\u2010Br\u2010cGMP were suppressed by cGMP\u2010dependent protein kinase G (PKG) inhibitor KT5823, indicating that PKG is a downstream signal mediator in the suppression of apoptosis by NO and cGMP. Both SNAP and 8\u2010Br\u2010cGMP induced endogenous Akt activation and Bad phosphorylation, resulting in the inhibition of Bad translocation to mitochondria;these effects were inhibited by KT5823 and the phosphatidylinositol 3\u2010kinase (PI3K) inhibitors LY294002 and Wortmannin. Our data suggest that the NO\/cGMP pathway suppresses 6\u2010OHDA\u2010induced PC12 cell apoptosis by suppressing the mitochon\u2010drial apoptosis signal via PKG\/PI3K\/Akt\u2010dependent Bad phosphorylation.\u2014Ha, K.\u2010S., Kim, K. M., Kwon, Y.\u2010G., Bai, S.\u2010K., Nam, W.\u2010D., Yoo, Y.\u2010M., Kim, P. K. M., Chung, H.\u2010T., Billiar, T. R., Kim, Y.\u2010M. Nitric oxide prevents 6\u2010hydroxydopamine\u2010induced apoptosis in PC12 cells through cGMP\u2010dependent PI3 kinase\/Akt activation.\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    17, 1036\u20131047 (2003)\n                  <\/jats:p>","DOI":"10.1096\/fj.02-0738com","type":"journal-article","created":{"date-parts":[[2003,5,28]],"date-time":"2003-05-28T19:06:21Z","timestamp":1054148781000},"page":"1036-1047","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":132,"title":["Nitric oxide prevents 6\u2010hydroxydopamine\u2010induced apoptosis in PC12 cells through cGMP\u2010dependent PI3 kinase\/Akt activation"],"prefix":"10.1096","volume":"17","author":[{"given":"KWON-SOO","family":"HA","sequence":"first","affiliation":[{"name":"Vascular System Research Center Department of Molecular and Cellular Biochemistry Kangwon National University School of Medicine Chunchon Kangwon-do Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"KI-MO","family":"KIM","sequence":"additional","affiliation":[{"name":"Vascular System Research Center Department of Molecular and Cellular Biochemistry Kangwon National University School of Medicine Chunchon Kangwon-do Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"YOUNG-GUEN","family":"KWON","sequence":"additional","affiliation":[{"name":"Vascular System Research Center Department of Molecular and Cellular Biochemistry Kangwon National University School of Medicine Chunchon Kangwon-do Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"SE-KYUNG","family":"BAI","sequence":"additional","affiliation":[{"name":"Vascular System Research Center Department of Molecular and Cellular Biochemistry Kangwon National University School of Medicine Chunchon Kangwon-do Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"WOO-DONG","family":"NAM","sequence":"additional","affiliation":[{"name":"Vascular System Research Center Department of Molecular and Cellular Biochemistry Kangwon National University School of Medicine Chunchon Kangwon-do Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"YOUNG-MIN","family":"YOO","sequence":"additional","affiliation":[{"name":"Vascular System Research Center Department of Molecular and Cellular Biochemistry Kangwon National University School of Medicine Chunchon Kangwon-do Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"PETER K. 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