Molecular Effects of Diphenyl Diselenide on Cholesterol and Glucose Cell Metabolism

J.T.   da   Rocha; L.      Trapani; M.      Segatto; P.   La   Rosa; C.W.      Nogueira; G.      Zeni; V.      Pallottini

Abstract

This study was designed to investigate the molecular effects of diphenyl diselenide ((PhSe)₂) on cholesterol metabolism in HepG2 cell line in a dose-dependent manner. The protein levels of both total and phosphorylated 3- hydroxy-3-methylglutaryl coenzyme A reductase (HMGR and P-HMGR), low-density lipoprotein receptors (LDLr) and the proteins involved in their regulatory network were analyzed by Western blotting, and the effect of (PhSe)₂ on HMGR activity was measured. Additionally, we also evaluated the effects of this compound on glucose transporter type 4 (GLUT4) translocation using fluorescence microscopy in L6 skeletal muscle cell line.

Results demonstrated that (PhSe)₂ increased P-HMGR, HMGR, and LDLr protein levels as well as simvastatin treatment, which was used as positive control, without directly affecting HMGR activity. We observed that both long- and short-term HMGR regulation mechanisms are involved in the effects of (PhSe)₂, as this compound was able to augment Sterol regulatory element binding proteins (SREBP)-1 and Insulin induced gene (Insig)1 protein levels, and to increase AMP activated kinase (AMPK) activation state. We also found that, in L6 skeletal myotubes, 10 μM (PhSe)₂ increases GLUT4 translocation through AMPK activation.

Taken together, these findings suggest that (PhSe)₂ can modulate the expression of some proteins involved in cholesterol and glucose cell metabolism.

Keywords: AMPK, cholesterol, diphenyl diselenide, glucose, HepG2 cells, L6 myoblasts, HMGR, LDLr.