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J.Health Sci., 48(5), 460-466, 2002
Suppression of Proteoglycan Synthesis by Calcium Ionophore A23187 in Cultured Vascular Endothelial Cells: Implication of Intracellular Calcium Accumulation in Lead Inhibition of Endothelial Proteoglycan Synthesis
Yasuyuki Fujiwara and Toshiyuki Kaji*
Department of Environmental Health, Faculty of Pharmaceutical Sciences, Hokuriku University, Ho-3 Kanagawa-machi, Kanazawa 920-1181, Japan
The purpose of the present study is to address the question of whether accumulation of intracellular calcium modulates the regulation of proteoglycan synthesis in vascular endothelial cells. Bovine aortic endothelial cells were treated with calcium ionophore A23187 in the presence of [35S]sulfate, and the labeled proteoglycans were analyzed by the cetylpyridinium chloride precipitation method and DEAE-Sephacel ion-exchange chromatography. The results showed that A23187 significantly decreases the accumulation of proteoglycans, especially heparan sulfate proteoglycans, in the cell layer and the conditioned medium of vascular endothelial cells. On the other hand, it was shown that lead, a heavy metal that inhibits endothelial heparan sulfate proteoglycan synthesis, significantly increased the intracellular calcium accumulation when the accumulation was assessed by calcium-45. The present data suggest that accumulation of intracellular calcium results in a suppression of heparan sulfate proteoglycan synthesis in vascular endothelial cells; the suppression may be one of the intracellular mechanisms for lead inhibition of endothelial heparan sulfate proteoglycan synthesis.
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