Effect of Lead on the Synthesis of Tissue Plasminogen Activator by Vascular Endothelial Cells in Culture
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概要
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To investigate the effect of lead on the synthesis of fibrinolytic proteins by vascular endothelial cells, cells obtained from human umbilical vein were exposed to the metal in a culture system. It was found that the secretion of tissue plasminogen activator (t-PA) is inhibited by lead but that of plasminogen activator inhibitor type 1 (PAI-1) was unaffected by the metal. However, gene expression of t-PA as well as PAI-1 was unaffected by lead when evaluated by quantitative reverse transcription-polymerase chain reaction. The inhibition of t-PA secretion by lead was observed even in the presence of actinomycin D, an inhibitor of mRNA synthesis. The inhibition of t-PA secretion by lead was also observed in the presence of the adenylate cyclase activator forskolin but was suppressed and disappeared in the presence of either 8-bromo adenosine 3', 5'-cyclic monophosphate that is a congener of adenosine 3', 5'-cyclic monophosphate which is resistant to degradation by phosphodiesterase or the phosphodiesterase inhibitor 1-methyl-3-isobutylxanthine. On the other hand, both the incorporation of [ ^<14>C] leucine into the acid-insoluble fraction of endothelial cells and the leakage of lactate dehydrogenase from the cells were unchanged by lead, indicating that the metal did not cause inhibition of general protein synthesis and nonspecific cell damage. The present data suggest that lead selectively inhibits t-PA synthesis by vascular endothelial cells at the post-transcriptional level and the inhibition is mediated by activation of the cyclic AMP-dependent pathway as a result of a lower activity of phosphodiesterase.
- 公益社団法人日本薬学会の論文
- 1999-06-30
著者
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Kaji Toshiyuki
Department Of Environmental Science Faculty Of Pharmaceutical Sciences Hokuriku University
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Yamamoto Chika
Department of Environmental Health, Faculty of Pharmaceutical Sciences, Hokuriku University
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Kaji Toshiyuki
Department Of Environmental Health Faculty Of Pharmaceutical Sciences Hokuriku University
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Yamamoto Chika
Department Of Environmental Health Faculty Of Pharmaceutical Sciences Hokuriku University
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