title: Delayed protection of tetramethylpyrazine on neonatal rat cardiomyocytes subjected to anoxia-reoxygenation injury.
abstract: The aim of this study was to investigate the cardioprotective effects and the possible mechanisms of delayed preconditioning induced by tetramethylpyrazine (TMP) in cultured neonatal rat cardiomyocytes subjected to anoxia-reoxygenation injury. Cultured neonatal rat cardiomyocytes were preconditioned using TMP at different concentrations (100, 200 and 500 microM). Cell viability, lactate dehydrogenase release, malondialdehyde formation, superoxide dismutase activity and glutathione peroxidase activity were measured to determine the protective effects against anoxia-reoxygenation injury. The expression of heat shock protein 70 (Hsp70) was measured 24 hr after TMP preconditioning by Western blot analysis. The results showed that TMP decreased lactate dehydrogenase release, increased cell viability, suppressed malondialdehyde formation and augmented activities of superoxide dismutase and glutathione peroxidase in a concentration-dependent manner. Moreover, the delayed protection was abolished by pre-treating with either protein kinase C inhibitor chelerythrine chloride or PD98059, a selective inhibitor of extracellular signal-regulated protein kinase 1/2, respectively, and the expression of Hsp70 was significantly increased in 24 hr after TMP preconditioning that was also suppressed by chelerythrine chloride or PD98059. These results suggest that TMP can induce delayed cardioprotective effects by activation of protein kinase C and extracellular signal-regulated protein kinase 1/2 signalling pathways and subsequent increased expression of Hsp70 in rat neonatal cardiomyocytes.
authors.affiliation: Key Laboratory of Food Science of Ministry of Education, Nanchang University, Nanchang, China.
authors.forename: He-Ping
authors.initials: HP
authors.lastname: Chen
authors.forename: Ming
authors.initials: M
authors.lastname: He
authors.forename: Qi-Ren
authors.initials: QR
authors.lastname: Huang
authors.forename: Guo-Hua
authors.initials: GH
authors.lastname: Zeng
authors.forename: Dan
authors.initials: D
authors.lastname: Liu
mesh_terms: D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D053119:Benzophenanthridines / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology; D005979:Glutathione Peroxidase / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D066298:In Vitro Techniques; D007770:L-Lactate Dehydrogenase / Q000096:biosynthesis; D008315:Malondialdehyde / Q000378:metabolism; D015428:Myocardial Reperfusion Injury / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000187:drug effects*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011719:Pyrazines / Q000494:pharmacology*; D051381:Rats; D013482:Superoxide Dismutase / Q000378:metabolism; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D000470:Alkaloids; D053119:Benzophenanthridines; D005419:Flavonoids; D018840:HSP70 Heat-Shock Proteins; D011719:Pyrazines; D014665:Vasodilator Agents; D008315:Malondialdehyde; C016299:chelerythrine; D007770:L-Lactate Dehydrogenase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D011493:Protein Kinase C; D048049:Extracellular Signal-Regulated MAP Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; C017953:tetramethylpyrazine