Nitric oxide-mediated the cardioprotection of tumor necrosis factor-alpha on cultured neonatal rat cardiomyocytes during hypoxia/reoxygenation
- VernacularTitle:NO介导TNF-?诱导的培养大鼠缺氧/复氧心肌细胞的保护作用
- Author:
Chen FU
;
Qiang XIA
;
Chunmei CAO
;
Jun YANG
;
Yuan LU
- Publication Type:Journal Article
- Keywords:
Myocardinm;
Tumor necrosis factor;
Anoxia;
Nitric oxide
- From:
Chinese Journal of Pathophysiology
2000;0(11):-
- CountryChina
- Language:Chinese
-
Abstract:
AIM: To investigate the role of nitric oxide synthase (NOS), soluble guanylyl cyclase (sGC) and protein kinase C (PKC) signaling in tumor necrosis factor-? (TNF-?)-induced cardioprotection against hypoxia/reoxygenation (H/R) injury. METHODS: Neonatal rat ventricular myocytes were pretreated with TNF-? or sodium nitroprusside (SNP) or L-arginine (L-Arg), respectively, for 12 h and then subjected to continuous hypoxia for 12 h, followed by reoxygenation for 6 h. The manganese superoxide dismutase (Mn-SOD) activity of the cells was measured after H/R. Myocyte injury was determined by the release of lactic dehydrogenase (LDH). RESULTS: TNF-? (10~5 (U/L)) significantly increased the Mn-SOD activity and decreased release of LDH from ventricular myocytes. The cardioprotection against H/R injury was induced by the pretreatment with SNP (5 ?mol/L) or L-Arg (5 mmol/L), which was blocked by ODQ (10 ?mol/L), the specific sGC inhibitor, and Chel (5 ?mol/L), the specific PKC inhibitor. Pretreatment with L-NAME (100 ?mol/L), ODQ, Chel, antoxidant 2-MPG (400 ?mol/L) or tyrosine kinase inhibitor genistein (50 ?mol/L) attenuated the increased Mn-SOD activity and reduced LDH level induced by TNF-?. CONCLUSION: The results suggest that NO may play a role in TNF-?-induced cardioprotection, which is mediated by sGC and PKC. [
