Effect of propofol on calcium homeostasis in hypoxia-reoxygenated neonatal rat cardiomyocytes.
Intracellular Ca2+ overload induced by hypoxia-reoxygenation alters Ca2+ homeostasis, which plays an important role in myocardial cell injury. Even though propofol is known as a radical scavenger with Ca2+ channel blocking properties, little is known about cardioprotective effect associated with Ca2+ homeostasis in cardiomyocytes. In the present study, we showed that propofol protects cardiomyocytes against hypoxia-reoxygenation injury. In propofol-treated cardiomyocytes, we observed a decrease in the expression of pro-apoptotic protein Bax, cytochrome c, caspase-3 activation and intracellular Ca2+ content. We also found that propofol treatment enhanced expression of anti-apoptotic protein Bcl-2 and activation of ERK concerned with survival. Propofol attenuated alterations of genes involving Ca2+-regulatory mechanism and significantly modulated abnormal changes of SERCA2a genes in hypoxia-reoxygenated neonatal cardiomyocytes. These results suggest that propofol modulates the expression of genes involved in Ca2+ homeostasis, thereby producing cardioprotective effects through a reduction in apoptotic cell death.
Kim
Hyun-Soo
HS
Brain Korea 21 Project for Medical Science, Yonsei University, Seoul 120-752, Republic of Korea.
Chang
Woo-Chul
WC
Hwang
Ki-Chul
KC
Choi
In-Geol
IG
Park
Wyun-Kon
WK
D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D053148:Caspase 3 / Q000378:metabolism; D015687:Cell Hypoxia / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D006706:Homeostasis / Q000187:drug effects*; D020287:In Situ Nick-End Labeling; D008297:Male; D018613:Microscopy, Confocal; D032383:Myocytes, Cardiac / Q000187:drug effects*; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics; D015742:Propofol / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects
D018686:Anesthetics, Intravenous; D002135:Calcium-Binding Proteins; D009419:Nerve Tissue Proteins; D053148:Caspase 3; D002118:Calcium; D015742:Propofol