title: Beneficial effect of taurine depletion on osmotic sodium and calcium loading during chemical hypoxia.
abstract: Cellular sodium excess is cytotoxic because it increases both the intracellular osmotic load and intracellular calcium concentration ([Ca(2+)](i)). Because sodium levels rise during hypoxia, it is thought to contribute to hypoxic injury. Thus the present study tested the hypothesis that taurine-linked reductions in [Na(+)](i) reduce hypoxia-induced cell injury. Taurine depletion was achieved by exposing isolated neonatal cardiomyocytes to medium containing the taurine analog beta-Alanine. As predicted, the beta-Alanine-treated cell exhibited less hypoxia-induced necrosis and apoptosis than the control, as evidenced by less swelling, shrinkage, TdT-mediated dUTP nick end labeling staining, and accumulation of trypan blue. After 1 h of chemical hypoxia, [Na(+)](i) was 3.5-fold greater in the control than the taurine-deficient cell. Although more taurine was lost from the control cell than from the beta-Alanine-treated cell during hypoxia, the combined taurine and sodium osmotic load was lower in the beta-Alanine-treated cell. Taurine deficiency also reduced the degree of hypoxia-induced calcium overload. Thus the observed resistance against hypoxia-induced necrosis and apoptosis is probably related to an improvement in sodium and calcium handling.
authors.affiliation: Department of Pharmacology, University of South Alabama School of Medicine, Mobile, Alabama 36688, USA. swschaffer@aol.com
authors.forename: Stephen W
authors.initials: SW
authors.lastname: Schaffer
authors.forename: Viktoriya
authors.initials: V
authors.lastname: Solodushko
authors.forename: David
authors.initials: D
authors.lastname: Kakhniashvili
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free; D006321:Heart / Q000187:drug effects; D006863:Hydrogen-Ion Concentration; D000860:Hypoxia / Q000139:chemically induced / Q000503:physiopathology*; D020287:In Situ Nick-End Labeling; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D009994:Osmolar Concentration; D051381:Rats; D012964:Sodium / Q000378:metabolism*; D013654:Taurine / Q000172:deficiency / Q000378:metabolism*; D015091:beta-Alanine / Q000494:pharmacology
chemical_list: D016895:Culture Media, Serum-Free; D015091:beta-Alanine; D013654:Taurine; D012964:Sodium; D002118:Calcium