[Effects of bisoprolol pretreatment on hypoxia/reoxygenation-induced injury in H9c2 cardiomyocytes].

OBJECTIVE: To investigated the effects of bisoprolol pretreatment on hypoxia/reoxygenation (H/R)-induced injury in H9c2 cardiomyocytes. METHODS: Cultured H9c2 cells were exposed to hypoxia for 6 h followed by reoxygenation for 2 h with or without pretreatments with bisoprolol or bisoprolol + LY294002. The cell survival was measured by MTT assay, and the cell apoptosis and levels of radical oxygen species (ROS) were evaluated with flow cytometry. The protein levels of phosphyorylated AKT and phosphorylated GSK3ß in the cells were determined by Western blotting. RESULTS: Compared with the normal control cells, the cells exposed to H/R injury showed significantly decreased cell survival and increased cell apoptosis and ROS production; pretreatment of the cells with bisoprolol significantly decreased the cell apoptotic rates and ROS production and obviously enhanced the cell survival and protein levels of p-AKT and p-GSK3ß in the exposed cells. The protective effect of bsioprolol against H/R-induced cell injury was significantly attenuated by LY294002. CONCLUSION: Bisoprolol can protect H9c2 cells against H/R-induced injury and oxidative stress by activating PI3K/AKT/Gsk-3ß pathway to increase the phosphorylation of AKT and GSK3ß and reduce ROS production.

Circulating cell-free mitochondrial deoxyribonucleic acid is increased in coronary heart disease patients with diabetes mellitus.

AIMS/INTRODUCTION: Circulating cell-free mitochondrial deoxyribonucleic acid (ccf-mtDNA) is presumably derived from injured tissues or cells in the body and has been suggested to be potential biomarker in several diseases. The present study explored whether mtDNA could be used as a biomarker to evaluate disease in coronary heart disease (CHD) patients with or without diabetes mellitus (DM). MATERIALS AND METHODS: A total of 50 CHD patients with type 2 diabetes, 50 CHD patients without type 2 diabetes, and 50 age- and sex-matched patients without CHD and DM (non-CHD-DM) were recruited. Ccf-mtDNA levels were assessed by measuring the nicotinamide adenine dinucleotide dehydrogenase 1 gene using quantitative real-time polymerase chain reaction. Receiver operating characteristic curve analysis of plasma mtDNA in CHD with or without DM was also determined. Multivariate logistic regression analyses were carried out to determine the correlation between the mtDNA levels and traditional CHD risk factors. RESULTS: The plasma ccf-mtDNA levels were significantly elevated in CHD patients with DM compared with those without and non-CHD-DM. The area under the receiver operating characteristic curves of mtDNA in CHD patients with DM vs non-CHD-DM was 0.907%. Correlation analyses of the mtDNA levels and traditional CHD risk factors showed that the mtDNA levels were significantly correlated with fasting blood glucose in CHD patients with DM. CONCLUSIONS: Ccf-mtDNA levels can be used as a biomarker in CHD patients with DM.

Berberine-induced apoptosis in human breast cancer cells is mediated by reactive oxygen species generation and mitochondrial-related apoptotic pathway.

Berberine has drawn extensive attention toward their wide range of biochemical and pharmacological effects, including antineoplastic effect in recent years, but the precise mechanisms remain unclear. Treatment of human breast cancer cells (MCF-7 and MDA-MB-231 cells) with berberine induced inhibition of cell viability in concentration- and time-dependent manner irrespective of their estrogen receptor (ER) expression. Hoechst33342 staining confirmed berberine induced breast cancer cell apoptosis in time-dependent manner. Because apoptosis induction is considered to be a crucial strategy for cancer prevention and therapy, berberine may be an effective chemotherapeutic agent against breast cancer. To explore the precise mechanism, berberine-induced oxidative stress and mitochondrial-related apoptotic pathway in human breast cancer cells were investigated in this study. In both MCF-7 and MDA-MB-231 cells, berberine increased the production of reactive oxygen species (ROS), which activated the pro-apoptotic JNK signaling. Phosphorylated JNK triggered mitochondria membrane potential (ΔΨm) depolarization and downregulation expression of anti-apoptotic protein Bcl-2 concomitant with the upregulation expression of pro-apoptotic protein Bax. Downregulation of anti-apoptotic Bcl-2 family protein in parallel with loss of ΔΨm, leading to increased the release of cytochrome c and apoptosis-inducing factor (AIF) from mitochondria, and eventually triggered the caspase-dependent and caspase-independent apoptosis. Taken together, our study reveled that berberine exerted an antitumor activity in breast cancer cells by reactive oxygen species generation and mitochondrial-related apoptotic pathway. These finding provide an insight into the potential of berberine for breast cancer therapy.