15-Deoxy- Δ(12,14)-prostaglandin J2 stabilizes hypoxia inducible factor-1α through induction of heme oxygenase-1 and direct modification ofprolyl-4-hydroxylase 2.

15-Deoxy-Δ(12,14)-prostaglandin J2 stabilizes hypoxia inducible factor-1α through induction of heme oxygenase-1 and direct modification ofprolyl-4-hydroxylase 2. Free Radic Res. 2016 Sep 6;:1-13 Authors: Choi JE, Kim JH, Song NY, Suh J, Kim DH, Kim SJ, Na HK, Nadas J, Dong Z, Cha YN, Surh YJ Abstract 15-Deoxy-Δ(12,14)-prostaglandin J2 (15d-PGJ2), a representative J-series cyclopentenone prostaglandin, has biphasic roles in cell proliferation and apoptosis. Hypoxia inducible factor-1 (HIF-1) regulates expression of various genes involved in tumor growth and angiogenesis. In the present study, treatment of human breast cancer (MCF-7) cells with 15d-PGJ2 resulted in the accumulation of the α-subunit of HIF-1. Pretreatment with zinc protoporphyrin IX, a pharmacological inhibitor of heme oxygenase-1 (HO-1), as well as siRNA knockdown of HO-1 gene in MCF-7 cells attenuated 15d-PGJ2-mediated HIF-1α accumulation. 15d-PGJ2 treatment increased intracellular production of reactive oxygen species (ROS), which was mediated by HO-1 induction. Preincubation of MCF-7 cells with trolox, a water-soluble form of vitamin E, attenuated 15d-PGJ2-induced HIF-1α expression although HO-1 expression was unchanged. This finding suggests that ROS accumulated as a consequence of HO-1 up-regulation can enhance HIF-1α expression in MCF-7 cells treated with 15d-PGJ2. Alternatively, 15d-PGJ2 was found to covalently bind to HIF-1α prolyl-4-hydroxylase 2 (PHD2...
Source: Free Radical Research - Category: Research Tags: Free Radic Res Source Type: research