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Patel JM, Block ER: Acrolein-induced injury to cultured pulmonary artery endothelial cells. . Toxicol Appl Pharmacol. 1993 Sep;122(1):46-53.
We evaluated the specific effects of acrolein on sulfhydryl status and plasma membrane-dependent functions of cultured pulmonary artery endothelial cells. Acrolein exposure caused a dose-dependent increase in lactate dehydrogenase (LDH) release and decreases in reduced glutathione (GSH) and protein sulfhydryl (P-SH) content, whereas oxidized glutathione (GSSG) content was not altered. Exposure to 4.5 microM, but not 1.5 or 3.0 microM, of acrolein caused significant (p < 0.05) LDH release. With increasing concentrations (25 microM) of acrolein, LDH release was increased to 66% (p < 0.001). Acrolein (3.0-25 microM) resulted in 36 to 100% reductions in GSH content, whereas reductions in P-SH content at these concentrations of acrolein ranged from 11 to 37%. Uptake of amino acids (cystine, glycine, and glutamic acid) and incorporation of valine into the protein fraction were significantly reduced in a dose-dependent fashion in acrolein (1.5-4.5 microM)-exposed cells. Reductions in cystine, glycine, and glutamic acid uptakes were maximal in cells exposed to 3 and 4.5 microM acrolein (p < 0.001). Similarly, maximum reductions (p < 0.001) in both uptake and incorporation of valine into the protein fraction were observed at 3.0 and 4.5 microM acrolein. Acrolein (1.5 microM) also resulted in significant loss of plasma membrane-specific Na+/K (+)-ATPase as well as plasma membrane P-SH content (p < 0.05 for both). When cells were treated with ouabain, reductions in amino acid uptake were observed, and this appeared to mimic the effect of acrolein exposure. When isolated plasma membranes were exposed to a known SH-alkylating agent, N-ethylmaleimide, losses of Na+/K (+)-ATPase and P-SH content were observed and were similar to the effects following exposure to acrolein. These results demonstrate that acrolein exposure results in alterations of plasma membrane-dependent transport in pulmonary artery endothelial cells, leading to reduced availability of precursor amino acids used in GSH and protein synthesis. This plasma membrane injury is accompanied by reductions in the GSH and P-SH contents of these cells. Loss of the plasma membrane P-SH appears to be associated with specific inactivation of Na+/K (+)-ATPase. |
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