title: Derangement of erythrocytic AE1 in beta-thalassemia by caspase 3: pathogenic mechanisms and implications in red blood cell senescence.
abstract: Considering its complex molecular pathophysiology, beta-thalassemia could be a good in vivo model to study some aspects related to erythrocyte functions with potential therapeutic implications not only within the frame of this particular hemoglobinopathy but also with respect to conditions in which the cellular milieu, altered by a deranged anion exchanger, could display a significant pathogenetic role (i.e., erythrocyte senescence, complications of red cell storage, renal tubular acidosis and some abnormal protein thesaurismosis). This work evaluates the anionic influx across band 3 protein in normal and beta-thalassemic red blood cells (RBCs) and ghosts. Since redox-mediated injury is an important pathway in the destruction of beta-thalassemic RBCs, we studied the anion transport and the activity of caspase 3 in the absence and presence of t-butylhydroperoxide in order to evaluate the effect of an increase of cellular oxidative stress. Interestingly, beta-thalassemic erythrocytes show a faster rate of anion exchange than normal RBCs and absence of any modulation mechanism of anion influx. These findings led us to formulate a hypothesis about the metabolic characteristics of beta-thalassemic erythrocytes, outlining that one of the main targets of caspase 3 in RBCs is the cytoplasmic domain of band 3 protein.
authors.affiliation: Department of Organic and Biological Chemistry, University of Messina, Messina, Italy.
authors.forename: Silvana
authors.initials: S
authors.lastname: Ficarra
authors.forename: Ester
authors.initials: E
authors.lastname: Tellone
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: Francesco
authors.initials: F
authors.lastname: Misiti
authors.forename: M Elisabetta
authors.initials: ME
authors.lastname: Clementi
authors.forename: Deborah
authors.initials: D
authors.lastname: Colucci
authors.forename: Ersilia
authors.initials: E
authors.lastname: Bellocco
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Laganà
authors.forename: Davide
authors.initials: D
authors.lastname: Barreca
authors.forename: Antonio
authors.initials: A
authors.lastname: Galtieri
mesh_terms: D001457:Anion Exchange Protein 1, Erythrocyte / Q000378:metabolism*; D053148:Caspase 3 / Q000378:metabolism*; D016922:Cellular Senescence / Q000502:physiology*; D004591:Electrophoresis, Polyacrylamide Gel; D004912:Erythrocytes / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D013431:Sulfates; D017086:beta-Thalassemia / Q000378:metabolism*
chemical_list: D001457:Anion Exchange Protein 1, Erythrocyte; D013431:Sulfates; D053148:Caspase 3