Assessment spermatogenic cell apoptosis and the transcript levels of metallothionein and p53 in Meretrix meretrix induced by cadmium.

Cadmium (Cd) has been widely used in industry and can accumulate in the water, soil, and food. Meretrix meretrix is one of the marine shellfishes cultivated for economic purpose in China. The increasing Cd levels in coastal marine water could adversely affect the economic benefits of shellfish cultivation. In the present study, M. meretrix were exposed to different Cd2+ concentrations (0, 1.5, 3, 6, and 12 mg L-1) for 5 d to evaluate the effects of Cd on spermatogenic cell. The Cd accumulation, survival rate and the indices of oxidative stress and apoptosis were determined in the spermatogenic cells of M. meretrix. The expression levels of p53 and metallothionein (MT) mRNA were also measured in the spermatogenic cells. Cd accumulation and the mortality rate of spermatogenic cells were found to increase in a dose-response manner with Cd2+ concentrations. Histopathology changes, especially the damage of membranous structure, were more severe as the Cd2+ levels in the testis became higher. The indexes of oxidative stress, including reactive oxygen species, malondialdehyde, protein carbonyl derivates and DNA-protein crosslinks all increased after exposure to Cd2+. However, the total antioxidant capacity gradually decreased with the increasing Cd2+ concentration. In addition, exposure to Cd2+ increased the apoptotic rate and caspase-3 and 9 activities but decreased the level of mitochondrial membrane potential and cytochrome C oxidase in the spermatogenic cells. MT mRNA expression increased in lower Cd2+ concentration treated groups whereas decreased in higher groups, while the p53 mRNA expression increased in a dose-response manner with Cd2+ and was positively correlated with the oxidative damage indices. These results indicated that Cd2+ caused oxidative stress and p53 induced apoptosis in the spermatogenic cells, and thus decreased the survival rate of sperm cells. This finding highlights that Cd can reduce the reproductive capacity of M. meretrix, thus threatening to wild shellfish populations and reducing the efficiency of shellfish farming.

Ablation of histone methyltransferase Suv39h2 in hepatocytes attenuates NASH in mice.

AIMS: Non-alcoholic steatohepatitis (NASH) is characterized by aberrant lipid metabolism in hepatocytes. We investigated the involvement of a histone H3K9 methyltransferase Suv39h2 in the pathogenesis of NASH. METHODS AND MATERIALS: NASH is induced by feeding the mice with a high-fat high-carbohydrate (HFHC) diet or a high-fat choline-deficient amino acid defined (HFD-CDAA) diet. The Suv39h2f/f mice were crossbred with the Alb-Cre mice to specifically delete Suv39h2 in hepatocytes. KEY FINDINGS: Ablation of Suv39h2 in hepatocytes improved insulin sensitivity of the mice fed either the HFHC diet or the CDAA-HFD diet. Importantly, Suv39h2 deletion significantly ameliorated NAFLD as evidenced by reduced lipid accumulation, inflammation, and fibrosis in the liver. RNA-seq uncovered Vanin-1 (Vnn1) as a novel transcriptional target for Suv39h2. Mechanistically, Suv39h2 repressed Vnn1 transcription in hepatocytes exposed to free fatty acids. Consistently, Vanin-1 knockdown normalized lipid accumulation in Suv39h2-null hepatocytes. Importantly, a significant correlation between Suv39h2, Vanin-1, and hepatic triglyceride levels was identified in NASH patients. SIGNIFICANCE: Our study uncovers a novel mechanism whereby Suv39h2 may contribute to NASH pathogenesis and suggests that targeting the Suv39h2-Vanin-1 axis may yield novel therapeutic solutions against NASH.