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Cardioprotection via modulation of calcium homeostasis by thiopental in hypoxia-reoxygenated neonatal rat cardiomyocytes
- Cardioprotection via modulation of calcium homeostasis by thiopental in hypoxia-reoxygenated neonatal rat cardiomyocytes
- Kim H.-S.; Hwang K.-C.; Park W.-K.
- Ewha Authors
- Issue Date
- Journal Title
- Yonsei Medical Journal
- vol. 51, no. 2, pp. 187 - 196
- SCI; SCIE; SCOPUS; KCI
- Purpose: Ca2+ homeostasis plays an important role in myocardial cell injury induced by hypoxia-reoxygenation, and prevention of intracellular Ca2+ overload is key to cardioprotection. Even though thiopental is a frequently used anesthetic agent, little is known about its cardioprotective effects, particulary in association with Ca2+ homeostasis. We investigated whether thiopental protects cardiomyocytes against hypoxia-reoxygenation injury by regulating Ca2+ homeostasis. Materials and Methods: Neonatal rat cardiomyocytes were isolated. Cardiomyocytes were exposed to different concentrations of thiopental and immediately replaced in the hypoxic chamber to maintain hypoxia. After 1 hour of exposure, a culture dish was transferred to the CO2 incubator and cells were incubated at 37°C for 5 hours. At the end of the experiments, the authors assessed cell protection using immunoblot analysis and caspase activity. The mRNA of genes involved in Ca2+ homeostasis, mitochondrial membrane potential, and cellular Ca2+ levels were examined. Results: In thiopental-treated cardiomyocytes, there was a decrease in expression of the proapoptotic protein Bax, caspase-3 activation, and intracellular Ca 2+ content. In addition, both enhancement of anti-apoptotic protein Bcl-2 and activation of Erk concerned with survival were shown. Furthermore, thiopental attenuated alterations of genes involving Ca2+ regulation and significantly modulated abnormal changes of NCX and SERCA2a genes in hypoxia-reoxygenated neonatal cardiomyocytes. Thiopental suppressed disruption of mitochondrial membrane potential (Δψm) induced by hypoxia-reoxygenation. Conclusion: Thiopental is likely to modulate expression of genes that regulate Ca2+ homeostasis, which reduces apoptotic cell death and results in cardioprotection. © Copyright: Yonsei University College of Medicine 2010.
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