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标题：Involvement of Ca2+/Calmodulin-Dependent Protein Kinase II in Heparin-Stimulated Release of Hepatic Lipase Activity from Rat Hepatocytes
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作者：Hisashi Tagashira ; Shinji Nakahigashi ; Rie Kerakawati 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：2005
卷号：28
期号：3
页码：409-412
DOI：10.1248/bpb.28.409
出版社：The Pharmaceutical Society of Japan
摘要：The release of hepatic lipase (HTGL), which is responsible for the hydrolysis of lipoprotein triacylglyceride, produced by heparin from the isolated rat hepatocytes in primary culture has been examined. Tyrosine kinase (TK) inhibitors (ST-638 and biochanin A) inhibited the heparin-stimulated release of HTGL activity. The activity of partially purified TK preparation from the hepatocytes was found to be increased following incubation with heparin in a manner which was both time- and dose-dependent. An intracellular Ca²⁺-chelator (Quin2/AM), a calmodulin inhibitor (W-7) and a Ca²⁺/calmodulin-dependent protein kinase II (CaMK-II) inhibitor (KN-93) suppressed the release of HTGL activity by heparin. In addition, CaMK-II activity in the hepatocytes incubated with heparin was recognized to elevate in a time- and dose-dependent manner. The increase in CaMK-II activity by heparin was markedly reduced in the presence of the inhibitors of TK. These results suggest that the release of HTGL activity from the hepatocytes by heparin is, in part, caused through a pathway involving an activation of CaMK-II associated with an increase in membrane TK activity.
关键词：hepatic lipase;Ca2+/calmodulin-dependent protein kinase II;tyrosine kinase;heparin;hepatocyte