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Melatonin reversed arginine vasopressin-induced apoptosis on H9c2 cardiomyoblasts by increasing Mst1-Nrf2 activity, yielding anti-oxidative enzyme up-regulation and lowered apoptosis; thus, it could serve as a potential heart failure treatment. [Display omitted] Heart failure patients have elevated arginine vasopressin (AVP) levels, which are involved in inducing peripheral vasoconstriction and cardiac hypertrophy. This hypertrophy, along with cardiomyocyte apoptosis, results from oxidative stress. Therefore, the antioxidant drug, melatonin (Mel), is commonly used to treat cardiac hypertrophy and apoptosis; however, whether it could alleviate AVP-induced myocardial injury remains to be addressed. In this study, high AVP doses were found to induce H9c2 cardiomyoblast apoptosis, demonstrated by increased terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive cells, pro-apoptotic B-cell lymphoma-2 (Bcl-2)-associated X protein (Bax) up-regulation, and anti-apoptotic Bcl-2 downregulation. This AVP-induced apoptotic increase, along with lowered cell viability, was also associated with higher reactive oxygen species (ROS) levels and lowered mitochondrial membrane potentials (MMP), which were all reversed upon Mel administration. Further investigations found that apoptosis, ROS, and MMP outcomes under high AVP were associated with Mst1-nuclear factor erythroid 2-related factor 2 (Nrf2) pathway suppression, yielding mitochondrial dysfunction, and Mel reversed them via promoting Mst1 phosphorylation, which then activated Nrf2 to increase anti-oxidative enzyme production. These findings were supported by siRNA gene suppression, where knocking down either Nrf2 or Mst1 abrogated the anti-apoptotic effects of Mel in cardiomyoblasts. Therefore, Mel could reduce cardiomyoblast apoptosis under high AVP levels, via Mst1-Nrf2 pathway re-activation, to enhance anti-oxidative responses. [ABSTRACT FROM AUTHOR]

Abstract: This study was designed to investigate the function of 17β-estradiol (17β-E2) against oxidative stress on the cell death of mice bone marrow mesenchymal stem cells (BMSCs) induced by hydrogen peroxide (H2O2). BMSCs were treated with 17β-E2 for 24h and then treated with 100μM H2O2 for 1h. Cell viability, apoptosis, caspase-9 mRNA, JNKs (Jun N-terminal kinases) and c-Jun protein expression in BMSCs were evaluated. Cell apoptosis of BMSCs were increased in a dose-dependent manner after treated with H2O2 compared to control group. But pretreatment with 17β-E2 can inhibit apoptosis of BMSCs, preserve the mitochondrial transmembrane potential, decrease caspase-9 mRNA, JNK1/2 and c-Jun protein expression. In conclusion, 17β-E2 exerts antiapoptotic effects in BMSCs which related to the mitochondria death pathway and JNKs pathway. The study revealed that 17β-E2 can reduce the donor stem cells damage. [Copyright &y& Elsevier]