title: Resveratrol alters the lipid composition, metabolism and peroxide level in senescent rat hepatocytes.
abstract: Investigations were performed on the influence of resveratrol on the lipid composition, metabolism, fatty acid and peroxide level in plasma membranes of hepatocytes, isolated from aged rats. Hepatocytes were chosen due to the central role of the liver in lipid metabolism and homeostasis. The obtained results showed that the level of sphingomyelin (SM) and phosphatidylserine (PS) was augmented in plasma membranes of resveratrol-treated senescent hepatocytes. The saturated/unsaturated fatty acids ratio of the two most abundant membrane phospholipids, phosphatidylcholine (PC) and phosphatidylethanolamine (PE), was decreased as a result of resveratrol treatment. The neutral sphingomyelinase was found to be responsible for the increase of SM and the decrease of ceramide in plasma membranes of resveratrol-treated senescent hepatocytes. Using labeled acetate as a precursor of lipid synthesis we demonstrated, that resveratrol treatment resulted in inhibition mainly of phospholipid synthesis, followed by fatty acids synthesis. Resveratrol induced reduction of specific membrane-associated markers of apoptosis such as localization of PS in the external plasma membrane monolayer and ceramide level. Finally, the content of lipid peroxides was investigated, because the unsaturated fatty acids, which were augmented as a result of resveratrol treatment, are an excellent target of oxidative attack. The results showed that the lipid peroxide level was significantly lower, ROS were slightly reduced and GSH was almost unchanged in resveratrol-treated hepatocytes. We suggest, that one possible biochemical mechanism, underlying the reported resveratrol-induced changes, is the partial inactivation of neutral sphingomyelinase, leading to increase of SM, the latter acting as a native membrane antioxidant. In conclusion, our studies indicate that resveratrol treatment induces beneficial alterations in the phospholipid and fatty acid composition, as well as in the ceramide and peroxide content in plasma membranes of senescent hepatocytes. Thus, the presented results imply that resveratrol could improve the functional activity of the membrane lipids in the aged liver by influencing specific membrane parameters, associated with the aging process.
authors.affiliation: Department of Lipid-Protein Interactions in Biomembranes, Institute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, Acad. G. Bonchev Str. Bl. 21, 1113 Sofia, Bulgaria. Electronic address: albena_momchilova@abv.bg.
authors.forename: Albena
authors.initials: A
authors.lastname: Momchilova
authors.affiliation: Department of Lipid-Protein Interactions in Biomembranes, Institute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, Acad. G. Bonchev Str. Bl. 21, 1113 Sofia, Bulgaria.
authors.forename: Diana
authors.initials: D
authors.lastname: Petkova
authors.affiliation: Department of Lipid-Protein Interactions in Biomembranes, Institute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, Acad. G. Bonchev Str. Bl. 21, 1113 Sofia, Bulgaria.
authors.forename: Galya
authors.initials: G
authors.lastname: Staneva
authors.affiliation: Department of Lipid-Protein Interactions in Biomembranes, Institute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, Acad. G. Bonchev Str. Bl. 21, 1113 Sofia, Bulgaria.
authors.forename: Tania
authors.initials: T
authors.lastname: Markovska
authors.affiliation: Department of Cytology, Histology and Embryology, Biological Faculty, Sofia University, 14, Dragan Cankov Str, 1164 Sofia, Bulgaria.
authors.forename: Roumen
authors.initials: R
authors.lastname: Pankov
authors.affiliation: Department of Cytology, Histology and Embryology, Biological Faculty, Sofia University, 14, Dragan Cankov Str, 1164 Sofia, Bulgaria.
authors.forename: Ralica
authors.initials: R
authors.lastname: Skrobanska
authors.affiliation: Department of Physiology, University of Kentucky, College of Medicine, Lexington, KY 40536, USA.
authors.forename: Mariana
authors.initials: M
authors.lastname: Nikolova-Karakashian
authors.affiliation: Department of Lipid-Protein Interactions in Biomembranes, Institute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, Acad. G. Bonchev Str. Bl. 21, 1113 Sofia, Bulgaria.
authors.forename: Kamen
authors.initials: K
authors.lastname: Koumanov
mesh_terms: D000085:Acetates / Q000378:metabolism; D000375:Aging / Q000378:metabolism*; D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism; D005453:Fluorescence; D005978:Glutathione / Q000378:metabolism; D022781:Hepatocytes / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism*; D050356:Lipid Metabolism / Q000187:drug effects*; D008054:Lipid Peroxides / Q000378:metabolism*; D008297:Male; D010713:Phosphatidylcholines / Q000378:metabolism; D010714:Phosphatidylethanolamines / Q000378:metabolism; D010718:Phosphatidylserines / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D000077185:Resveratrol; D013107:Sphingolipids / Q000378:metabolism; D013267:Stilbenes / Q000494:pharmacology*
chemical_list: D000085:Acetates; D005227:Fatty Acids; D008054:Lipid Peroxides; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; D010718:Phosphatidylserines; D017382:Reactive Oxygen Species; D013107:Sphingolipids; D013267:Stilbenes; C483858:phosphatidylethanolamine; D005978:Glutathione; D000077185:Resveratrol
keywords: Aging; Hepatocytes; Membrane lipids; Oxidative stress; Resveratrol