Signal transduction of nitric oxide donor-induced protection in hydrogen peroxide-mediated apoptosis in H9C2 cardiomyoblasts

被引:21
作者
Chae, HJ
Kim, HR
Kwak, YG
Ko, JK
Joo, CU
Chae, SW [1 ]
机构
[1] Chonbuk Natl Univ, Sch Med, Dept Pharmacol, Inst Cardiovasc Res, Jeonju 560180, South Korea
[2] Wonkwang Univ, Sch Dent, Dept Dent Pharmacol, Iksan 570749, Chonbuk, South Korea
关键词
D O I
10.1081/IPH-100103859
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Nitric oxide (NO) attenuates hydrogen peroxide (H2O2)-mediated injury to H9C2 cardiomyoblasts. To examine the role of nitric oxide, cultured H9C2 cardiomyoblasts were treated with H2O2 for 2 h in the presence or absence of the NO donor, diethylamine nitric oxide (DEANO). DEANO (30 muM) attenuated H2O2-induced apoptosis in H9C2 cells. H2O2-exposed H9C2 cells resulted in apoptosis in a time-dependent manner estimated by DNA fragmentation assay, nuclear morphology stained with fluorescent dye, Hoechst 33258 and Annexin V staining. Pretreatment with z-VAD-FMK, a pancaspase inhibitor, or z-DEVD-CHO, a specific caspase-3 inhibitor, completely suppressed the DNA ladder in response to H2O2. An increase in caspase-3-like protease (DEVDase) activity was observed during apoptosis, but no caspase-1 activity (YVADase) was detected. Treatment of H9C2 cells with 100 muM H2O2 resulted in a strong activation of JNK/SAPK. However, the activation of JNK/SAPK was clearly attenuated by 30 muM DEANO. Furthermore, the dominant negative JNK and SEK1-expressing cells displayed a marked decrease in number of apoptotic cells. This inhibition of JNK1 in the system is involved in the protection of H2O2-induced apoptosis in H9C2 cardiomyoblasts.
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页码:187 / 204
页数:18
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