title: Acidic preconditioning protects endothelial cells against apoptosis through p38- and Akt-dependent Bcl-xL overexpression.
abstract: To analyze the underlying cellular mechanisms of adaptation to ischemia-induced apoptosis through short acidic pretreatment, i.e. acidic preconditioning (APC), Wistar rat coronary endothelial cells (EC) were exposed for 40 min to acidosis (pH 6.4) followed by a 14 h recovery period (pH 7.4) and finally treated for 2 h with simulated in vitro ischemia (glucose-free anoxia at pH 6.4). APC led to a transient activation of p38 and Akt kinases, but not of JNK and ERK1/2 kinases, which was accompanied by significant reduction of the apoptotic cell number, caspase-12/-3 cleavage and Bcl-xL overexpression. These effects of APC were completely abolished by prevention of Akt- or p38-phosphorylation during APC. Furthermore, knock-down of Bcl-xL by siRNA-transfection also abolished the anti-apoptotic effect of APC. Therefore, APC leads to protection of EC against ischemic apoptosis by activation of Akt and p38 followed by overexpression of Bcl-xL, which is a key anti-apoptotic mechanism of APC.
authors.affiliation: Department of Clinical Pharmacology, Ruhr-University Bochum, Universitätsstr. 150, 44801 Bochum, Germany.
authors.forename: Jan-Paul
authors.initials: JP
authors.lastname: Flacke
authors.forename: Sanjeev
authors.initials: S
authors.lastname: Kumar
authors.forename: Sawa
authors.initials: S
authors.lastname: Kostin
authors.forename: H Peter
authors.initials: HP
authors.lastname: Reusch
authors.forename: Yury
authors.initials: Y
authors.lastname: Ladilov
mesh_terms: D000818:Animals; D017209:Apoptosis; D053454:Caspase 12 / Q000378:metabolism; D042783:Endothelial Cells / Q000201:enzymology*; D015971:Gene Expression Regulation, Enzymologic; D006863:Hydrogen-Ion Concentration; D019194:Ischemic Preconditioning; D008297:Male; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D051020:bcl-X Protein / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D034741:RNA, Small Interfering; D051020:bcl-X Protein; D051057:Proto-Oncogene Proteins c-akt; D048051:p38 Mitogen-Activated Protein Kinases; D053454:Caspase 12