title: Oxidative effects of gemfibrozil on anion influx and metabolism in normal and Beta-thalassemic erythrocytes: physiological implications.
abstract: To further clarify some peculiar molecular mechanisms related to the physiology and pathophysiology of erythrocytes with respect to oxygen binding and release, metabolism and senescence, we investigated the oxidative effects of gemfibrozil in normal and beta-thalassemic red blood cells. Our results showed that the oxidative stress promoted by the drug, through a direct interaction with hemoglobin, may lead to activation of caspase 3, which in turn influences the band 3 anion flux and glucose metabolism. In a comparative context, we also evaluated the effect on band 3 and caspase 3 activation of orthovanadate (a phosphatase inhibitor) and t-butylhydroperoxide (a known oxidant). The results support the hypothesis that gemfibrozil influences band 3 function through several mechanisms of action, centered on oxidative stress, which induces significant alterations of glucose metabolism.
authors.affiliation: Organic and Biological Chemistry Department, University of Messina, Salita Sperone 31, Messina, Italy. etellone@isengard.unime.it
authors.forename: Ester
authors.initials: E
authors.lastname: Tellone
authors.forename: Silvana
authors.initials: S
authors.lastname: Ficarra
authors.forename: Bruno
authors.initials: B
authors.lastname: Giardina
authors.forename: Roberto
authors.initials: R
authors.lastname: Scatena
authors.forename: Annamaria
authors.initials: A
authors.lastname: Russo
authors.forename: M Elisabetta
authors.initials: ME
authors.lastname: Clementi
authors.forename: Francesco
authors.initials: F
authors.lastname: Misiti
authors.forename: Ersilia
authors.initials: E
authors.lastname: Bellocco
authors.forename: Antonio
authors.initials: A
authors.lastname: Galtieri
mesh_terms: D000328:Adult; D001457:Anion Exchange Protein 1, Erythrocyte / Q000378:metabolism; D000838:Anions / Q000378:metabolism*; D053148:Caspase 3 / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D004912:Erythrocytes / Q000187:drug effects* / Q000378:metabolism; D015248:Gemfibrozil / Q000494:pharmacology*; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D000960:Hypolipidemic Agents / Q000494:pharmacology; D017136:Ion Transport / Q000187:drug effects; D007700:Kinetics; D008875:Middle Aged; D008954:Models, Biological; D018384:Oxidative Stress / Q000187:drug effects; D014638:Vanadates / Q000494:pharmacology; D017086:beta-Thalassemia / Q000097:blood*
chemical_list: D001457:Anion Exchange Protein 1, Erythrocyte; D000838:Anions; D006454:Hemoglobins; D000960:Hypolipidemic Agents; C454201:SLC4A1 protein, human; D014638:Vanadates; D053148:Caspase 3; D015248:Gemfibrozil