NS398 protects cells from sodium nitroprusside-mediated cytotoxicity through enhancing HO-1 induction independent of COX-2 inhibition
- Authors
- Nizamutdinova, Irina Tsoy; Lee, Jae Heun; Seo, Han Geuk; Chang, Ki Churl; Kim, Hye Jung
- Issue Date
- Jan-2009
- Publisher
- PHARMACEUTICAL SOC KOREA
- Keywords
- HO-1; COX-2; SNP; NS398; Adaptive response
- Citation
- ARCHIVES OF PHARMACAL RESEARCH, v.32, no.1, pp.99 - 107
- Indexed
- SCIE
SCOPUS
KCI
- Journal Title
- ARCHIVES OF PHARMACAL RESEARCH
- Volume
- 32
- Number
- 1
- Start Page
- 99
- End Page
- 107
- URI
- https://scholarworks.bwise.kr/gnu/handle/sw.gnu/26442
- DOI
- 10.1007/s12272-009-1123-3
- ISSN
- 0253-6269
- Abstract
- Heme oxygenase-1 (HO-1) plays a preventive role in oxidative stress. In contrast, COX-2 is involved in the pathogenesis of many inflammatory diseases, thus COX-2 inhibitor is believed to exert anti-inflammatory properties by blocking COX-2. Recently, however, salicylate the active metabolite of aspirin showed COX-independent anti-inflammatory effects through induction of HO-1. Thus, we hypothesized that HO-1 are induced as an adaptive response to sodium nitroprusside (SNP) and play a protective role against cytotoxicity. Moreover, we investigated the protective effect of NS398 known as a selective COX-2 inhibitor on SNP-mediated cytotoxicity, and whether the protective effect of NS398 is due to COX-2 inhibition or not. SNP induced cytotoxicity in a dose-dependent manner, which was enhanced by inhibition of HO-1, suggesting that HO-1 acts in an adaptive response to SNP. Interestingly, NS398 decreased SNP-mediated cytotoxicity whereas COX-2 siRNA did not. Furthermore, NS398 enhanced SNP-induced HO-1 induction even though NS398 alone failed to induce HO-1 protein expression. In addition, NS398 enhanced SNP-induced COX-2, even though NS398 effectively inhibited SNP-mediated PGE(2) production. These results demonstrate that NS398 exerts cytoprotective effects by inducing HO-1 independent of COX-2 inhibition.
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