Beneficial effect of taurine depletion on osmotic sodium and calcium loading during chemical hypoxia.
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.
Schaffer
Stephen W
SW
Department of Pharmacology, University of South Alabama School of Medicine, Mobile, Alabama 36688, USA. swschaffer@aol.com
Solodushko
Viktoriya
V
Kakhniashvili
David
D
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
D016895:Culture Media, Serum-Free; D015091:beta-Alanine; D013654:Taurine; D012964:Sodium; D002118:Calcium