To investigate the protective effects of genistein (Gen) on tert-butyl hydroperoxide (TBHP)-induced H9c2 cell aging and its mechanism, H9c2 cells were randomly divided into control group, model group (200 μmol/L TBHP) and low, medium and high dose Gen groups (0.04, 0.2 and 1 μmol/L of Gen, respectively). The survival rate was determined by the MTT method. Cell senescence was observed by β-galactosidase (SA-β-gal) staining. The total antioxidant capacity (T-AOC), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT) activities, and malondialdehyde (MDA) content were determined by the colorimetric assay. The expressions of P53, P21, Kelch-like epichlorohydrin-related protein-1(Keap1), nuclear factor E2-related factor (Nrf2) and heme oxygenase 1(HO-1) proteins, and the phosphorylation of phosphatidylinositol-3-kinase (PI3K), protein kinase B (AKT), extracellular regulatory protein kinase1/2 (ERK1/2), P38 mitogen-activated protein kinase (P38) and c-jun amino-terminal kinase (JNK) were detected with the western blotting method. Compared with the model group, the survival rate was increased, the positive staining of SA-β-gal was decreased; T-AOC, SOD, GSH-Px and CAT activities were increased, and MDA content was decreased in Gen groups. Meanwhile, Gen down-regulated the Keap1 protein expression and up-regulated the Nrf2 and HO-1 protein expressions. Gen also increased the expressions of P53, P21 proteins, elevated the phosphorylation of PI3K and AKT proteins, and reduced the phosphorylation of ERK, P38 and JNK proteins. Gen could delay the cell senescence and improve the antioxidant capacity in H9c2 cells. The mechanism may be related to the up-regulation of Nrf2 through PI3K/AKT and MAPKs signaling pathways.
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