| Summary: | 碩士 === 國立成功大學 === 藥理學研究所 === 90 === Eukayotic transcription is a highly regulated process, and histone acetylation is now known to play a major role in this regulation. Acetylation of histone N-termini reduces chromatin condensation; thus gene transcription may activate. Previously, we found that c-Jun induction was required in epidermal growth factor (EGF) induced human 12(S)-lipoxygenase (12(S)-LOX) gene expression in human epidermoid carcinoma A431 cells. In this study, we studied the effect of histone deacetylase inhibitors, trichostatin A (TSA) and sodium butyrate (NaBT) on EGF induced expression of 12(S)-LOX. TSA could enhance the acetylation level of histone H4 within one hour. In order to study the effect of TSA and NaBT on EGF-induced expression of 12(S)-LOX, the 12(S)-LOX enzyme activity was determined. TSA and NaBT inhibited EGF-induced 12(S)-LOX enzyme activity in a dose-dependent manner. Both inhibitors did not have any significant effects on phosphorylation of ERK and JNK, induced by EGF. In the in vitro kinase assay, TSA and NaBT decreased JNK activity in cells, but not ERK activity. Both TSA and NaBT reduced EGF-induced N-terminal phosphorylation and expression of c-Jun. Furthermore, in cells overexpression of c-Jun mutant (N 1-220), which contains c-Jun N-terminal 1-220 amino acids, we found that TSA inhibited EGF-induced c-Jun Ser63 and Ser73 phosphorylation of c-Jun mutant (N 1-220). These results suggest that the inhibition of TSA and NaBT on EGF-induced the expression of 12(S)-LOX was due to inhibit JNK activity and then attenuate N-terminal phosphorylation of c-Jun, which led to the inhibition of c-Jun expression.
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