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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Lasunción, Miguel A. Sánchez-wandelmer, Jana Giera, Martin Cano, Sonia Dávalos, Alberto Herrera, Emilio De La Peña, Gema Busto, Rebeca |
| Description | Author Affiliation: Sánchez-Wandelmer J ( Servicio de Bioquímica-Investigación, Hospital Ramón y Cajal, Madrid, Spain.) |
| Abstract | Lipid rafts are plasma membrane microdomains that are highly enriched with cholesterol and sphingolipids and in which various receptors and other proteins involved in signal transduction reside. In the present work, we analyzed the effect of cholesterol biosynthesis inhibition on lipid raft/caveolae composition and functionality and assessed whether sterol precursors of cholesterol could substitute for cholesterol in lipid rafts/caveolae. 3T3-L1 preadipocytes were treated with distal inhibitors of cholesterol biosynthesis or vehicle (control) and then membrane rafts were isolated by sucrose density gradient centrifugation. Inhibition of cholesterol biosynthesis with either SKF 104976, AY 9944, 5,22-cholestadien-3β-ol or triparanol, which inhibit different enzymes on the pathway, led to a marked reduction in cholesterol content and accumulation of different sterol intermediates in both lipid rafts and non-raft domains. These changes in sterol composition were accompanied by disruption of lipid rafts, with redistribution of caveolin-1 and Fyn, impairment of insulin-Akt signaling and the inhibition of insulin-stimulated glucose transport. Cholesterol repletion abrogated the effects of cholesterol biosynthesis inhibitors, reflecting they were specific. Our results show that cholesterol is required for functional raft-dependent insulin signaling. |
| ISSN | 00063002 |
| Journal | Biochimica et Biophysica Acta (BBA) - Reviews on Cancer |
| Issue Number | 9 |
| Volume Number | 1788 |
| Language | English |
| Publisher | Elsevier |
| Publisher Date | 2009-09-01 |
| Publisher Place | Netherlands |
| Access Restriction | Open |
| Subject Keyword | Caveolae Drug Effects Cell Membrane Metabolism Cholesterol Biosynthesis Membrane Microdomains 3T3-L1 Cells Animals Caveolin 1 Dehydrocholesterols Pharmacology Enzyme Inhibitors G(M1) Ganglioside Lanosterol Analogs & Derivatives Mice Receptor, Insulin Triparanol Trans-1,4-Bis(2-chlorobenzaminomethyl)cyclohexane Dihydrochloride Research Support, Non-U.S. Gov't Biochemistry |
| Content Type | Text |
| Resource Type | Article |
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