Baicalein protects chicken embryonic cardiomyocyte against hypoxia-reoxygenation injury via mu- and delta- but not kappa-opioid receptor signaling.
Baicalein, a pure compound derived from Scutellaria baicalensis Georgi, protected cells from lethal damage in an ischemia-reperfusion model. This study was aimed to investigate the role of opioid receptors in mediating cardioprotection by baicalein against hypoxia-reoxygenation injury. By using chick cardiomyocyte as in vitro model, baicalein was added to the perfusate during 1 h-hypoxia followed by 1 h-reoxygenation. Cell viability was assessed by propidium iodide uptake, while apoptosis was assessed by TUNEL and Hoechst 33342 staining. The expression of opioid receptors mRNA in chicken embryonic myocardium was determined by RT-PCR. Opioid receptor antagonists, protein kinase C inhibitors, and KATP channel blockers were used to determine the presumed signal transduction pathways. The results showed that baicalein (0.1 approximately 5 microM) concentration dependently reduced hypoxia-reoxygenation-induced myocardial death and apoptosis. The cardioprotective effect of baicalein (1 microM) was blocked by pretreatment of nonspecific opioid receptor antagonist (naloxone), opioid mu-receptor (beta-funaltrexamine) and delta-receptor (7-Benzylidenenaltrexone) antagonists, protein kinase C inhibitors (H7 and chelerythrine), and KATP channel blockers (glibenclamide and 5-hydroxydecanoate). Finally, RT-PCR analysis successfully demonstrated the presence of opioid receptors mRNA in chicken embryonic cardiomyocytes. We conclude that the cardioprotective effect of baicalein is mediated via mu-, delta- but not kappa-opioid receptor and their related signal transduction pathways, such as protein kinase C and the KATP channel.
Tu
I-Hua
IH
Institute of Traditional Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC.
Yen
Hung-Tsang David
HT
Cheng
Hui-Wen
HW
Chiu
Jen-Hwey
JH
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001092:Arachidonate 12-Lipoxygenase / Q000502:physiology; D002642:Chick Embryo; D019610:Cytoprotection; D044950:Flavanones / Q000494:pharmacology*; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D032383:Myocytes, Cardiac / Q000187:drug effects*; D015221:Potassium Channels / Q000502:physiology; D011493:Protein Kinase C / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis; D017465:Receptors, Opioid, delta / Q000235:genetics / Q000502:physiology*; D017473:Receptors, Opioid, kappa / Q000235:genetics / Q000502:physiology*; D017450:Receptors, Opioid, mu / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*
D044950:Flavanones; D015221:Potassium Channels; D012333:RNA, Messenger; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; C117780:mitochondrial K(ATP) channel; C006680:baicalein; D001092:Arachidonate 12-Lipoxygenase; D011493:Protein Kinase C