当前位置: X-MOL 学术J. Nutr. Biochem. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Curcumin induces expression of 15-hydroxyprostaglandin dehydrogenase in gastric mucosal cells and mouse stomach in vivo: AP-1 as a potential target.
The Journal of Nutritional Biochemistry ( IF 5.6 ) Pub Date : 2020-07-29 , DOI: 10.1016/j.jnutbio.2020.108469
Jeong-Hwa Woo 1 , Jong-Min Park 2 , Ji-Hye Jang 1 , Hongkyung Yang 3 , Young-Joon Surh 4 , Hye-Kyung Na 5
Affiliation  

15-Hydroxyprostaglandin dehydrogenase (15-PGDH) catalyzes the conversion of oncogenic prostaglandin E2 to non-tumerigenic 15-keto prostaglandin E2. In the present study, we found that curcumin, a yellow coloring agent present in the rhizome of Curcuma longa Linn (Zingiberaceae), induced expression of 15-PGDH at the both transcriptional and translational levels in normal rat gastric mucosal cells. By using deletion constructs of 15-PGDH promoter, we were able to demonstrate that activator protein-1 (AP-1) is the principal transcription factor responsible for regulating curcumin-induced 15-PGDH expression. Curcumin enhanced the expression of c-Jun and c-Fos that are functional subunits of AP-1, in the nuclear fraction of cells. Silencing of c-Jun suppressed curcumin-induced expression of 15-PGDH. Moreover, the chromatin immunoprecipitation assay revealed curcumin-induced binding of c-Jun to the AP-1 consensus sequence present in the 15-PGDH promoter. Curcumin increased phosphorylation of ERK1/2 and JNK, and pharmacologic inhibition of these kinases abrogated the curcumin-induced phosphorylation of c-Jun and 15-PGDH expression. In contrast, tetrahydrocurcumin which lacks the α,β-unsaturated carbonyl group failed to induce 15-PGDH expression, suggesting that the electrophilic carbonyl group of curcumin is essential for its induction of 15-PGDH expression. Curcumin restored the expression of 15-PGDH which is down-regulated by Helicobacter pylori through suppression of DNA methyltransferase 1. In addition, oral administration of curcumin increased the expression of 15-PGDH and its regulators such as p-ERK1/2, p-JNK, and c-Jun in the mouse stomach. Taken together, these findings suggest that curcumin-induced upregulation of 15-PGDH may contribute to chemopreventive effects of this phytochemical on inflammation-associated gastric carcinogenesis.



中文翻译:

姜黄素在体内诱导胃粘膜细胞和小鼠胃中15-羟前列腺素脱氢酶的表达:AP-1作为潜在靶标。

15-羟基前列腺素脱氢酶(15-PGDH)催化致癌性前列腺素E 2向非致瘤性15-酮前列腺素E 2的转化。在本研究中,我们发现姜黄素(一种姜黄素)存在于姜黄姜科)的根茎中),在正常大鼠胃粘膜细胞中在转录和翻译水平上诱导15-PGDH的表达。通过使用15-PGDH启动子的缺失构建体,我们能够证明激活蛋白1(AP-1)是负责调节姜黄素诱导的15-PGDH表达的主要转录因子。姜黄素增强了细胞核部分中AP-1的功能性亚基c-Jun和c-Fos的表达。c- jun的沉默抑制姜黄素诱导的15-PGDH表达。此外,染色质免疫沉淀试验显示姜黄素诱导c-Jun与15-PGDH启动子中存在的AP-1共有序列结合。姜黄素增加ERK1 / 2和JNK的磷酸化,并且这些激酶的药理抑制作用废除了姜黄素诱导的c-Jun和15-PGDH表达的磷酸化。相反,缺乏α,β-不饱和羰基的四氢姜黄素不能诱导15-PGDH表达,这表明姜黄素的亲电羰基对于诱导15-PGDH表达是必不可少的。姜黄素恢复了幽门螺杆菌下调的15-PGDH表达通过抑制DNA甲基转移酶1。此外,口服姜黄素可增加15-PGDH及其调节剂(例如p-ERK1 / 2,p-JNK和c-Jun)在小鼠胃中的表达。综上所述,这些发现表明姜黄素诱导的15-PGDH上调可能有助于这种植物化学物质对炎症相关胃癌的化学预防作用。

更新日期:2020-07-29
down
wechat
bug