COX-2 regulates the insulin-like growth factor 1-induced potentiation of Zn2+-toxicity in primary cortical culture

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dc.contributor.authorJ Y Im-
dc.contributor.authorD Y Kim-
dc.contributor.authorK W Lee-
dc.contributor.authorJ B Kim-
dc.contributor.authorJ K Lee-
dc.contributor.authorDong Sik Kim-
dc.contributor.authorYoung Ik Lee-
dc.contributor.authorK S Ha-
dc.contributor.authorC O Joe-
dc.contributor.authorP L Han-
dc.date.accessioned2017-04-19T09:01:23Z-
dc.date.available2017-04-19T09:01:23Z-
dc.date.issued2004-
dc.identifier.issn0026-895X-
dc.identifier.uri10.1124/mol.66.3.ko
dc.identifier.urihttps://oak.kribb.re.kr/handle/201005/6602-
dc.description.abstractThe pretreatment of cultured cortical neurons with neurotrophic factors markedly potentiates the cytotoxicity induced by low concentrations of Zn2+ or excitotoxins. In the current study, we investigated the mechanism underlying the insulin-like growth factor- I (IGF-I)-induced Zn2+ toxicity potentiation. The pretreatment of primary cortical cultures for more than 12 h with 100 ng/ml of IGF-I increased the cytotoxicity induced by 80 μM Zn2+ by more than 2-fold. The IGF-I.enhanced cell death was blocked by the COX-2.specific inhibitors N-[2-(cyclohexyloxyl)-4-nitrophenyl]- methane sulfonamide (NS-398; 10.100 μM) and 1-[(4-methylsulfonyl) phenyl]-3-trifluoro-methyl-5-[(4-fluoro)phenyl]pyrazole (SC58125; 10 μM) and by the antioxidant trolox (30 μM). In addition, it was observed that COX-2 expression was increased 12 to 24 h after IGF-I treatment. Preincubation of cortical cultures with IGF-I increased arachidonic acid (AA)-induced cytotoxicity, and AA increased Zn2+ toxicity, which suggested the involvement of COX activity in these cellular responses. Moreover, enhanced COX-2 activity led to a decrease in the cell’s reducing power, as indicated by a gradual depletion of intracellular GSH. Cortical neurons pretreated with IGF-I and then Zn2+ showed consistently enhanced reactive oxygen species production, which was repressed by NS-398 and SC58125. Cortical neurons treated with Zn2+ and then AA displayed the increased ROS production, which was also suppressed by NS-398 and SC58125. These results suggest that COX-2 is an endogenous factor responsible for the IGF-I.induced potentiation of Zn2+ toxicity and that enhanced COX-2 activity leads to a decrease in the cell’s reducing power and an increase in ROS accumulation in primary cortical cultures.-
dc.publisherAmer Soc Pharmacology Experimental Therapeutics-
dc.titleCOX-2 regulates the insulin-like growth factor 1-induced potentiation of Zn2+-toxicity in primary cortical culture-
dc.title.alternativeCOX-2 regulates the insulin-like growth factor 1-induced potentiation of Zn2+-toxicity in primary cortical culture-
dc.typeArticle-
dc.citation.titleMolecular Pharmacology-
dc.citation.number3-
dc.citation.endPage376-
dc.citation.startPage368-
dc.citation.volume66-
dc.contributor.affiliatedAuthorDong Sik Kim-
dc.contributor.affiliatedAuthorYoung Ik Lee-
dc.contributor.alternativeName임주영-
dc.contributor.alternativeName김도연-
dc.contributor.alternativeName이강우-
dc.contributor.alternativeName김정빈-
dc.contributor.alternativeName이자경-
dc.contributor.alternativeName김동식-
dc.contributor.alternativeName이영익-
dc.contributor.alternativeName하권수-
dc.contributor.alternativeName조철오-
dc.contributor.alternativeName한평림-
dc.identifier.bibliographicCitationMolecular Pharmacology, vol. 66, no. 3, pp. 368-376-
dc.identifier.doi10.1124/mol.66.3.-
dc.description.journalClassY-
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