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- Title
Hypoxia-inducible regulation of placental BOK expression.
- Authors
Daochun LUO; Isabella CANIGGIA; POST, Martin
- Abstract
BOK (BCL-2-related ovarian killer) is a member of the proapoptotic BCL-2 family that is highly expressed in the human placenta.BOKexcess causes increased trophoblast autophagy and apoptosis in pre-eclampsia, a pathological condition of hypoxia and oxidative stress. In the present study, we identified an HRE (hypoxia-response element) at the junction of exon-1 and intron- 1 (+229 to +279) in the human BOK gene, as well as an antisense transcript driven by a promoter located in intron-2. The isolated BOK-HRE bound hypoxia-inducible HIF (hypoxiainducible factor) proteins in vitro as well as in trophoblastic JEG3 cells and was functional in its natural position as well as in front of a heterologous promoter. Being a reverted repeat, the BOK-HRE functioned in both orientations. This directionless feature of the BOK-HRE facilitates hypoxia regulation via HIF of both BOK and its antisense transcript as demonstrated by RNAi knockdown of the HIF system. Although the antisense transcript was expressed in several human carcinoma cell lines, including choriocarcinoma-derived JEG3 cells, no antisenseregulated mechanism for BOK expression was noted. Taken together, these findings indicate that hypoxia-induced expression of BOK in placental cells is regulated via HIF and is not affected by its antisense transcript.
- Subjects
HYPOXEMIA; GENETIC regulation; GENETIC code; PLACENTA; AUTOPHAGY; APOPTOSIS; ANTISENSE RNA
- Publication
Biochemical Journal, 2014, Vol 461, Issue 3, p391
- ISSN
0264-6021
- Publication type
Article
- DOI
10.1042/BJ20140066