title: Alpinetin activates the δ receptor instead of the κ and μ receptor pathways to protect against rat myocardial cell apoptosis.
abstract: Alpinetin is a natural flavonoid that protects cells against fatal injury in ischemia-reperfusion. δ receptor activation protects myocardial cells from trauma; however, the mechanism is unknown. The aim of this study was to explore the function of alpinetin in δ receptor-mediated myocardial apoptosis. The myocardial cells of newly born rats were cultivated and myocardial apoptosis was induced by serum deprivation. The MTT method was used to evaluate cell viability and Annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI) staining was used to analyze apoptosis. The expression levels of opioid receptor mRNA and protein were tested using reverse transcription-polymerase reaction (RT-PCR) and western blot assays. In addition, an opioid receptor antagonist, as well as protein kinase C (PKC) and extracellular signal-regulated kinase (ERK) inhibitors, were used to determine the inferred signaling pathway. The results showed that that alpinetin reduced the myocardial apoptosis induced by serum deprivation in a concentration-dependent manner. However, the protection conferred to the myocardial cells by alpinetin was blocked by the δ opioid receptor antagonist naltrindole, as well as by PKC and ERK inhibitors (GF109203X and U0126, respectively). In addition, it was shown that alpinetin was able to maintain the stability of the mitochondrial membrane potential, lower the level of intracytoplasmic cytochromecand reduce Bax displacement from the cytoplasm to the mitochondria. It was concluded that alpinetin was able to activate δ receptors to induce the endogenous protection of myocardial cells via the PKC/ERK signaling pathway.
authors.affiliation: Department of Cardiology, Daqing General Hospital Group Oilfield General Hospital, Daqing, Heilongjiang 163000, P.R. China.
authors.forename: Chuantao
authors.initials: C
authors.lastname: Suo
authors.affiliation: Department of Gastrointestinal Surgery, China-Japan Union Hospital, Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Libo
authors.initials: L
authors.lastname: Sun
authors.affiliation: Department of Cardiology, Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Yang
keywords: PKC/ERK pathways; alpinetin; apoptosis; cardiomyocytes; δ receptor