| Research Abstract |
1. Phorbol 12-myristate 13-acetate (PMA) down regulated the level of MDR3 mRNA in human Chang liver cells in a time- and concentration-dependent manner. A specific inhibitor of protein kinase C (PKC), GF109203X, inhibited the action of PMA. From these results, it was indicated that the level MDR3 mRNA was down-regulated by the PKC dependent cell signaling system.
2. The cellular level of MDR3 mRNA was increased by the treatment with doxorubicin, and the increment was decreased by antioxidants. Then it was suggested that doxorubicin enhanced the level of MDR3 mRNA level through the production of reactive oxygen species.
3. The cellular level of MDR3 mRNA in Chang liver cells was decreased by the treatment with tumor necrosis factor alpha (TNFalpha) in a time- and concentration-dependent manner. This decrease was antagonized by the inhibitors of PKC and mitogen-activated protein kinase (MAPK) kinase. From these results, it was suggested that the decrease of MDR3 mRNA level by TNFalpha was induced through PKC and MAPK.
4. The cellular level of MDR3 mRNA in Chang liver cells was decreased by the treatment with an activator of protein kinase A, forskolin, and the decrease was inhibited by an inhibitor of protein kinase A, H-89. Thus it was suggested that protein kinase A negatively regulated the level of MDR3 mRNA in Chang liver cells.
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