15-Keto prostaglandin E2 induces heme oxygenase-1 expression through activation of Nrf2 in human colon epithelial CCD 841 CoN cells.

摘要: Prostaglandin E2 (PGE2) plays a key role in inflammation-associated carcinogenesis. NAD+-dependent 15-hydroxyprostaglandin dehydrogenase (15-PGDH) catalyzes the oxidation of 15(S)-hydroxyl group PGE2 to generate 15-keto PGE2. 15-PGDH has been known as tumor suppressor various malignancies including colon cancer. However, molecular mechanisms underlying tumor-suppressive function remain largely unresolved. In this study, we found that upregulated expression heme oxygenase-1 (HO-1), representative antioxidative and anti-inflammatory enzyme, at both transcriptional translational levels, human epithelial CCD 841 CoN cells. A redox-sensitive transcription factor, NF-E2-related factor (Nrf2) critical regulation HO-1 other cytoprotective proteins. 15-Keto induced translocation Nrf2 into nucleus antioxidant response element-driven luciferase activity. Furthermore, silencing gene abolished PGE2-induced activated AKT signaling, pharmacological inhibitor, LY294002 suppressed expression. generates reactive oxygen species which is by general N-acetyl-l-cysteine. N-acetyl-l-cysteine treatment attenuated phosphorylation GSK3β, activity Nrf2, subsequently 13,14-dihydro-15-keto lacking α,β-unsaturated carbonyl moiety failed induce intracellular production species, nuclear Nrf2. conclusion, induces through activation