Title : Increase of CYP1A1 mRNA and AHH activity by inhibitors of either protein or RNA synthesis in mouse hepatocytes in primary culture.

Pub. Date : 1991 Nov

PMID : 1934297






7 Functional Relationships(s)
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1 After temporary treatment of hepatocytes for 10 h with cycloheximide, an inhibitor of protein synthesis, AHH activity measured 14 h later was at a normal low level, although medium-change-associated CYP1A1 mRNA were increased by cycloheximide treatment. Cycloheximide cytochrome P450, family 1, subfamily a, polypeptide 1 Mus musculus
2 After temporary treatment of hepatocytes for 10 h with cycloheximide, an inhibitor of protein synthesis, AHH activity measured 14 h later was at a normal low level, although medium-change-associated CYP1A1 mRNA were increased by cycloheximide treatment. Cycloheximide cytochrome P450, family 1, subfamily a, polypeptide 1 Mus musculus
3 After temporary treatment of hepatocytes for 10 h with cycloheximide, an inhibitor of protein synthesis, AHH activity measured 14 h later was at a normal low level, although medium-change-associated CYP1A1 mRNA were increased by cycloheximide treatment. Cycloheximide cytochrome P450, family 1, subfamily a, polypeptide 1 Mus musculus
4 However, if cells were treated with either actinomycin D, alpha-amanitin or cordycepin, which are inhibitors of RNA synthesis, after exposure to cycloheximide, prominent induction of AHH activity was observed, the levels being almost equal to those for hepatocytes treated with benz[a]anthracene, a potent AHH inducer. Cycloheximide cytochrome P450, family 1, subfamily a, polypeptide 1 Mus musculus
5 However, if cells were treated with either actinomycin D, alpha-amanitin or cordycepin, which are inhibitors of RNA synthesis, after exposure to cycloheximide, prominent induction of AHH activity was observed, the levels being almost equal to those for hepatocytes treated with benz[a]anthracene, a potent AHH inducer. Cycloheximide cytochrome P450, family 1, subfamily a, polypeptide 1 Mus musculus
6 After washing out cycloheximide and/or benz[a]anthracene, the decrease in the mRNA amounts was delayed in the presence of actinomycin D and half amounts were found even 12 h later; while without actinomycin D they reduced with a half-life of 3-4 h. The observations indicate that CYP1A1 gene expression might be regulated at the post-transcriptional level with compensatory mRNA stabilization under conditions of blocked further production, resulting in elevation of AHH activity. Cycloheximide cytochrome P450, family 1, subfamily a, polypeptide 1 Mus musculus
7 After washing out cycloheximide and/or benz[a]anthracene, the decrease in the mRNA amounts was delayed in the presence of actinomycin D and half amounts were found even 12 h later; while without actinomycin D they reduced with a half-life of 3-4 h. The observations indicate that CYP1A1 gene expression might be regulated at the post-transcriptional level with compensatory mRNA stabilization under conditions of blocked further production, resulting in elevation of AHH activity. Cycloheximide cytochrome P450, family 1, subfamily a, polypeptide 1 Mus musculus