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KMID : 0370020020160000025
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Chung-Ang Journal of Pharmacal Sciences
2002 Volume.16 No. 0 p.25 ~ p.30
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Effect of Protein Kinase Inhibitor on Silica-induced Free Radical Generation in RAW 264.7 Cells
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Abstract
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To investigate involvement of protein kinase in reactive oxygen species (ROS) and peroxynitrite (PON) generation, we examined effect of protein kinase inhibitors on silica-induced ROS and PON generation in RAW 264.7 cells. Silica dose-dependently increased ROS and PON generation. Protein kinase C inhibitor, bisindolmaleimide and RO32-0432, slightly inhibited silica-induced ROS generation and significantly inhibited PON generation. Tyrosine kinase inhibitor, erbstatin and DHC, significantly inhibited silica-induced ROS generation but not PON generation. Calmodulin antagonist (W-7), calmodulin-dependent protein kinase Ⅱ inhibitor (KN-62) and mitogen-activated protein kinase inhibitor (PD98059) significantly inhibited silica-induced PON generation but not ROS generation. These results suggest that protein kinase C appears to be involved in both ROS and PON generation, tyrosine kinase in ROS generation, and calmodulin antagonist and mitogen-activated protein kinase in PON generation induced by silica in RAW 264.7 cells.
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KEYWORD
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