title: Molecular effects of diphenyl diselenide on cholesterol and glucose cell metabolism.
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.
authors.affiliation: Department of Science, University Roma Tre, Viale Marconi, 446, 00146- Rome, Italy. valentina.pallottini@uniroma3.it.
authors.forename: J T
authors.initials: JT
authors.lastname: da Rocha
authors.forename: L
authors.initials: L
authors.lastname: Trapani
authors.forename: M
authors.initials: M
authors.lastname: Segatto
authors.forename: P
authors.initials: P
authors.lastname: La Rosa
authors.forename: C W
authors.initials: CW
authors.lastname: Nogueira
authors.forename: G
authors.initials: G
authors.lastname: Zeni
authors.forename: V
authors.initials: V
authors.lastname: Pallottini
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000818:Animals; D001555:Benzene Derivatives / Q000494:pharmacology*; D015153:Blotting, Western; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D005947:Glucose / Q000378:metabolism*; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism; D015394:Molecular Structure; D018482:Muscle, Skeletal / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D016566:Organoselenium Compounds / Q000494:pharmacology*; D010766:Phosphorylation; D021381:Protein Transport / Q000187:drug effects; D051381:Rats; D011973:Receptors, LDL / Q000378:metabolism; D051779:Sterol Regulatory Element Binding Proteins / Q000378:metabolism
chemical_list: D001555:Benzene Derivatives; D051275:Glucose Transporter Type 4; D016566:Organoselenium Compounds; D011973:Receptors, LDL; D051779:Sterol Regulatory Element Binding Proteins; C061132:diphenyldiselenide; D002784:Cholesterol; D006903:Hydroxymethylglutaryl CoA Reductases; D055372:AMP-Activated Protein Kinases; D005947:Glucose