Studies on the Regulatory System Governing Tissue Type-plasminogen Activator Gene Expression in Primary Cultured Rat Hepatocytes
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The role of cAMP/cAMP dependent protein kinase (A-kinase) system in the regulation of hepatic tissue-type plasminogen activator (h-tPA) production was studied by use of primary cultured rat hepatocytes. Cholera toxin (CT) which is known to elevate intracellular cAMP concentration, augmented h-tPA production in a dosage-dependent manner. Hepatic-tPA mRNA expression was also augmented to 220% of the control by 10-7M CT. A protein kinase inhibitor H-8, which preferably inhibits A-kinase, lowered the level augmented by CT to the control level, and actinomycin D was completely inhibited h-tPA expression. Cycloheximide, a protein synthesis inhibitor, brought marked accumulation of h-tPA mRNA rather than inhibition of the h-tPA expression. These data showed that the de novo protein synthesis is not necessary for the augmentation mechanism, and suggest that the existence of a repressor protein for h-tPA gene.
- 一般社団法人 日本血栓止血学会の論文
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