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Division of Nephrology, Department of Medicine, Medical University of South Carolina, Charleston, South Carolina (Q.Y.); Laboratory of Molecular and Cellular Biomedicine, Associate Unit of the Instituto de la Grasa (Consejo Superior de Investigaciones Científicas), Department of Biology, IUNICS, University of the Balearic Islands, Palma de Mallorca, Spain (R.A., J.C., K.K., P.V.E.); and Department of Pharmacology, Louisiana State University Health Sciences Center, New Orleans, Louisiana (S.M.L.)
We have recently reported that lipid structure regulates the interaction with membranes, recruitment to membranes, and distribution to membrane domains of heterotrimeric G
proteins, G subunits, and G dimers (J Biol Chem 279:36540–36545, 2004). Here, we demonstrate that modulation of the membrane structure not only determines G protein localization but also regulates the function of G proteins and related signaling proteins. In this context, the antitumor drug daunorubicin (daunomycin) and oleic acid changed the membrane structure and inhibited G protein activity in biological membranes. They also induced marked changes in the activity of the 2A/D-adrenergic receptor and adenylyl cyclase. In contrast, elaidic and stearic acid did not change the activity of the above-mentioned proteins. These fatty acids are chemical but not structural analogs of oleic acid, supporting the structural basis of the modulation of membrane lipid organization and subsequent regulation of G protein-coupled receptor signaling. In addition, oleic acid (and also daunorubicin) did not alter G protein activity in a membrane-free system, further demonstrating the involvement of membrane structure in this signal modulation. The present work also unravels in part the molecular bases involved in the antihypertensive (Hypertension 43:249–254, 2004) and anticancer (Mol Pharmacol 67:531–540, 2005) activities of synthetic oleic acid derivatives (e.g., 2-hydroxyoleic acid) as well as the molecular bases of the effects of diet fats on human health.
Address correspondence to: Dr. Pablo V. Escribá, Laboratory of Molecular and Cellular Biomedicine, Department of Biology, IUNICS, University of the Balearic Islands, Ctra. de Valldemossa km 7.5, E-07122 Palma de Mallorca, Spain. E-mail: pablo.escriba{at}uib.es
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  S. Teres, G. Barcelo-Coblijn, M. Benet, R. Alvarez, R. Bressani, J. E. Halver, and P. V. Escriba Oleic acid content is responsible for the reduction in blood pressure induced by olive oil PNAS, September 16, 2008; 105(37): 13811 - 13816. [Abstract] [Full Text] [PDF]
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 F. Barcelo, J. Prades, J. A. Encinar, S. S. Funari, O. Vogler, J. M. Gonzalez-Ros, and P. V. Escriba Interaction of the C-Terminal Region of the G{gamma} Protein with Model Membranes Biophys. J., October 1, 2007; 93(7): 2530 - 2541. [Abstract] [Full Text] [PDF]
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