Inhibitory effect of oleanolic acid on 12-O-tetradecanoylphorbol-13-acetate-induced gene expression in mouse skin
Inhibitory effect of oleanolic acid on 12-O-tetradecanoylphorbol-13-acetate-induced gene expression in mouse skin
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DOI：
10.1006/toxs.1998.2485
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发表时间：
1998-09-01
影响因子：
3.8
通讯作者：
Yoshida, T
中科院分区：
文献类型：
--
作者：
Oguro, T;Liu, J;Yoshida, T
齐墩果酸（OA）已被证明能抑制12- o -十四烷醇-13-乙酸酯（TPA）对小鼠皮肤肿瘤的促进作用。本研究旨在探讨OA对tpa诱导的鸟氨酸脱羧酶（ODC）基因及其他基因表达的影响。OA抑制TPA对雌性CD-1小鼠皮肤ODC活性和mRNA水平的诱导作用。将OA （10 μ mol）预先应用于小鼠背侧皮肤，可使TPA （8 nmol）诱导的表皮ODC活性和ODC基因表达降低约50%。这些结果表明OA主要在转录水平抑制tpa诱导的ODC。除ODC外，TPA还可刺激小鼠皮肤金属硫蛋白（MT）基因表达，2.5 μ mol OA可使TPA诱导的MT mRNA表达降低50%。在TPA （8 nmol）处理后，OA （10 μ mol）处理也抑制了ODC和MT基因的表达，这表明OA不与TPA竞争其受体。OA预处理对c-fos基因表达也有抑制作用。这些结果表明，OA可以减少TPA的一些信号转导通路，从而抑制小鼠皮肤中靶基因的表达。本研究提示OA可能是抑制tpa刺激小鼠皮肤基因表达的一般抑制剂。(C) 1998毒理学学会。
Oleanolic acid (OA) has been shown to inhibit mouse skin tumor promotion by 12-O-tetradecanoylphorbol-13-acetate (TPA). This study was designed to examine the effect of OA on the TPA-induced expression of the ornithine decarboxylase (ODC) gene as well as other genes. OA inhibited the induction of ODC activity and mRNA level produced by TPA in the skin of female CD-1 mice. Preapplication of OA (10 mu mol) to the mouse dorsal skin produced an approximately 50% decrease in TPA (8 nmol)-induced epidermal ODC activity, as well as ODC gene expression. These results suggest that OA inhibits TPA-induced ODC mainly at the transcriptional level. In addition to ODC, TPA also stimulated metallothionein (MT) gene expression in mouse skin, A dose of 2.5 mu mol of OA diminished the TPA-induced MT mRNA 50%. Treatment with OA (10 mu mol) after TPA (8 nmol) application also inhibited ODC and MT gene expression which suggests that OA does not compete with TPA for its receptor. OA pretreatment also prevented c-fos gene expression. All of these findings suggest that OA diminishes some signal transduction pathways of TPA to suppress target gene expression in mouse skin. This study suggests that OA might be a general inhibitor against TPA-stimulated gene expression in mouse skin. (C) 1998 Society of Toxicology.