Oxidative effects of gemfibrozil on anion influx and metabolism in normal and Beta-thalassemic erythrocytes: physiological implications.
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.
Tellone
Ester
E
Organic and Biological Chemistry Department, University of Messina, Salita Sperone 31, Messina, Italy. etellone@isengard.unime.it
Ficarra
Silvana
S
Giardina
Bruno
B
Scatena
Roberto
R
Russo
Annamaria
A
Clementi
M Elisabetta
ME
Misiti
Francesco
F
Bellocco
Ersilia
E
Galtieri
Antonio
A
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*
D001457:Anion Exchange Protein 1, Erythrocyte; D000838:Anions; D006454:Hemoglobins; D000960:Hypolipidemic Agents; C454201:SLC4A1 protein, human; D014638:Vanadates; D053148:Caspase 3; D015248:Gemfibrozil