Abstract:

Objective  To observe the effect of simvastatin (Sim) on the  production  of beta-amyloid peptide (Aβ) via RhoA/ROCK pathway. Methods  HEK293 cells transferred with β-secretase(BACE1) were cultured in vitro with cholesterol sufficient culture medium and divided into five groups: control group, 1μmol/L Sim group, 1μmol/L Sim +250μmol/L mevalonic acid(Mev) group, 5μmol/L Sim group, 5μmol/L Sim + 250μmol/L Mev group. MTT was employed to identify the vitality of the cells; ELISA was used for detecting extracellular Aβ42; Western blotting was employed to detect the expression of  RhoA in cell membrane and  phosphorylated myosin-binding subunit of myosin phosphatase (p-MYPT1 ) in cytoplasm. Results  All treatment groups had no effects on the vitality of BACE1-HEK293 cells(P>0.05). Compared with control group, the secreted Aβ42 was decreased in 1μmol/L and 5μmol/L Sim groups (P<0.05). The expression of  RhoA in cell membrane and p-MYPT1 in cytoplasm were both decreased in 1μmol/L and 5μmol/L Sim groups(P<0.01), and 250μmol/L Mev could reversed the effect of Sim(P<0.01). Conclusion  Simvastatin decreases not only the RhoA in cell membrane together with p-MYPT1 in cytoplasm, but also the secretion of Aβ42 via cholesterol-independent mechanism.

Key words: Beta-amyloid peptide; Simvastatin; RhoA protein; Rho kinase; Mevalonic acid