Prostaglandin E2 is involved in the increase of cytochrome P-450 2B1 expression by alpha-tocopherol succinate in primary rat hepatocytes in the presence of phenobarbital
2001
Tsai, C.F. | Lii, C.K. | Yang, J.J. | Liu, K. | Lin, W.L. | Chen, H.W.
The modulation of cytochrome P-450 2B1 expression by alpha-tocopheryl succinate and whether prostaglandin E2 is involved in this modulation in primary rat hepatocytes in the presence of phenobarbital were investigated. A primary rat hepatocyte culture model that faithfully reproduces the phenobarbital response observed in vivo was used. Intracellular alpha-tocopherol content was dose dependently increased by alpha-tocopheryl succinate incubation. Hepatocytes were demonstrated to have prostaglandin E2-synthesizing capability. alpha-Tocopheryl succinate inhibited prostaglandin E2 synthesis by hepatocytes and increased cytochrome P-450 2B1 expression in the presence of phenobarbital; however, it had little effect on intracellular cAMP level. To mimic the exogenous source of prostaglandin E2 from nonparenchymal cells, various concentrations of prostaglandin E2 were added to the cell culture. High doses of exogenous prostaglandin E2 (100 and 1,000 nM) inhibited the cytochrome P-450 2B1 expression in the presence of phenobarbital compared with low doses (1 and 10 nM); however, the presence of high doses of prostaglandin E2 had no effect on intracellular cAMP level. Forskolin significantly increased intracellular cAMP level and inhibited cytochrome P-450 2B1 expression in the presence of phenobarbital. The results of this study indicate that alpha-tocopheryl succinate increases cytochrome P-450 2B1 expression via its inhibition of prostaglandin E2 synthesis in the presence of phenobarbital; however, changes in intracellular cAMP level are not related to cytochrome P-450 2B1 expression.
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