Cardioprotection Via Modulation of Calcium Homeostasis by Thiopental in Hypoxia-Reoxygenated Neonatal Rat Cardiomyocytes.
10.3349/ymj.2010.51.2.187
- Author:
Hyun Soo KIM
1
;
Ki Chul HWANG
;
Wyun Kon PARK
Author Information
1. Department of Life Science, College of Natural Sciences, Ewha Womans University, Seoul, Korea.
- Publication Type:Original Article
- Keywords:
Thiopental;
Ca2+ homeostasis;
hypoxia-reoxygenation;
cardiomyocytes
- MeSH:
Animals;
Apoptosis;
Calcium/*metabolism;
Cell Hypoxia/*physiology;
Cell Survival/drug effects;
Cells, Cultured;
GABA Modulators/*pharmacology;
Homeostasis/drug effects;
Immunoblotting;
In Situ Nick-End Labeling;
Membrane Potential, Mitochondrial/drug effects;
Microscopy, Confocal;
Myocytes, Cardiac/*drug effects/*metabolism;
Rats;
Rats, Sprague-Dawley;
Reverse Transcriptase Polymerase Chain Reaction;
Thiopental/*pharmacology
- From:Yonsei Medical Journal
2010;51(2):187-196
- CountryRepublic of Korea
- Language:English
-
Abstract:
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 37degrees 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 Ca2+ 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 (Delta Psi m) 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.
