title: Gab1 Is Modulated by Chronic Hypoxia in Children with Cyanotic Congenital Heart Defect and Its Overexpression Reduces Apoptosis in Rat Neonatal Cardiomyocytes.
abstract: Gab1 (Grb2 associated binding protein 1) is a member of the scaffolding/docking proteins (Gab1, Gab2, and Gab3). It is required for fibroblast cell survival and maintaining cardiac function. Very little is known about human Gab1 expression in response to chronic hypoxia. The present study examined the hypothesis that hypoxia regulates Gab1 expression in human paediatric myocardium and cultured rat cardiomyocytes. Here we showed that Gab1 is expressed in myocardial tissue in acyanotic and cyanotic children with congenital heart defects. Gab1 protein was upregulated in cyanotic compared to acyanotic hearts suggesting that Gab1 upregulation is a component of the survival program initiated by hypoxia in cyanotic children. The expression of other Gab1 interacting partners was not affected by hypoxia and Gab1 regulation. Additionally, using an in vitro model, we demonstrated that overexpressing Gab1 in neonatal cardiomyocytes, under hypoxic condition, resulted in the reduction of apoptosis suggesting a role for this protein in cardiomyocyte survival. Altogether, our data provide strong evidence that Gab1 is important for heart cell survival following hypoxic stress.
authors.affiliation: Bristol Heart Institute, School of Clinical Sciences, University of Bristol, Research Level 7, Bristol Royal Infirmary, Upper Maudlin Street, Bristol BS2 8HW, UK.
authors.forename: Myriam
authors.initials: M
authors.lastname: Cherif
authors.affiliation: Bristol Heart Institute, School of Clinical Sciences, University of Bristol, Research Level 7, Bristol Royal Infirmary, Upper Maudlin Street, Bristol BS2 8HW, UK ; RUSH University Medical Center, Chicago, IL 60612, USA.
authors.forename: Massimo
authors.identifier: 0000-0001-7508-0891
authors.initials: M
authors.lastname: Caputo
authors.affiliation: Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Nakaoka
authors.affiliation: Bristol Heart Institute, School of Clinical Sciences, University of Bristol, Research Level 7, Bristol Royal Infirmary, Upper Maudlin Street, Bristol BS2 8HW, UK.
authors.forename: Gianni D
authors.initials: GD
authors.lastname: Angelini
authors.affiliation: Bristol Heart Institute, School of Clinical Sciences, University of Bristol, Research Level 7, Bristol Royal Infirmary, Upper Maudlin Street, Bristol BS2 8HW, UK.
authors.forename: Mohamed T
authors.initials: MT
authors.lastname: Ghorbel
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000096:biosynthesis* / Q000235:genetics; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D006321:Heart / Q000254:growth & development*; D006330:Heart Defects, Congenital / Q000235:genetics* / Q000503:physiopathology; D006801:Humans; D000860:Hypoxia / Q000235:genetics; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009206:Myocardium / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology; D010750:Phosphoproteins / Q000096:biosynthesis* / Q000235:genetics; D051381:Rats
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C098587:GAB1 protein, human; C490896:Gab1 protein, rat; D010750:Phosphoproteins