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.
Molecular effects of diphenyl diselenide on cholesterol and glucose cell metabolism / da Rocha, J. T; Trapani, L; Segatto, Marco; La Rosa, P; Nogueira, C. W; Zeni, G; Pallottini, V.. - In: CURRENT MEDICINAL CHEMISTRY. - ISSN 1875-533X. - ELETTRONICO. - 20:35(2013), pp. 4426-4434. [10.2174/0929867311320350007]
Molecular effects of diphenyl diselenide on cholesterol and glucose cell metabolism
SEGATTO, MARCO;La Rosa, P;
2013
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.File | Dimensione | Formato | |
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