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Decreased lectin-like oxidized LDL receptor 1 (LOX-1) and low Nrf2 activation in placenta are involved in preeclampsia.
- Source :
-
The Journal of clinical endocrinology and metabolism [J Clin Endocrinol Metab] 2012 Oct; Vol. 97 (10), pp. E1862-70. Date of Electronic Publication: 2012 Jul 12. - Publication Year :
- 2012
-
Abstract
- Context: Serum concentration of oxidized low-density lipoprotein (oxLDL) is higher in women with preeclampsia than in normal pregnant woman. Lectin-like oxLDL receptor-1 (LOX-1) is one of the scavenger receptors for oxLDL and is abundantly expressed in placenta. It is well known that oxLDL activates nuclear factor erythroid 2-related factor 2 (Nrf2), a master regulator of antioxidant and cytoprotective genes such as heme oxygenase-1 (HO-1), which play an important role in preeclampsia. However, it has yet to be elucidated whether LOX-1, along with Nrf2, participates in the pathology of preeclampsia.<br />Objective: The objective of the study was to assess LOX-1 expression and Nrf2 activation in preeclamptic placentas and to manifest their physiological roles in preeclampsia.<br />Methods: Expression and regulation of LOX-1, HO-1, and Nrf2 were evaluated by real-time quantitative RT-PCR and Western blotting. The functions of LOX-1 and Nrf2 were examined using an anti-LOX-1 antibody and Nrf2 activator in JAR, a choriocarcinoma cell line, and placental explants.<br />Results: Both LOX-1 expression and Nrf2 activation were significantly decreased in preeclamptic placentas compared with normal controls. A significant decrease in LOX-1 mRNA was found in placental explant cultures under hypoxic conditions. Activation of Nrf2 up-regulated HO-1 in both the JAR cells and placental explants. Furthermore, oxLDL increased HO-1 mRNA, whereas the blockade of LOX-1 inhibited the increase of HO-1 mRNA in JAR cells.<br />Conclusion: Decreasing LOX-1 expression in preeclamptic placenta may contribute to high oxLDL concentration, low Nrf2 activation, and low HO-1 expression. These findings provide novel insights into the crucial role of LOX-1 and Nrf2 in the pathogenesis of preeclampsia.
- Subjects :
- Adult
Antioxidants metabolism
Cell Line, Tumor
Choriocarcinoma
Chorionic Villi metabolism
Chorionic Villi pathology
Female
Heme Oxygenase-1 genetics
Heme Oxygenase-1 metabolism
Humans
Hypoxia metabolism
Hypoxia pathology
NF-E2-Related Factor 2 genetics
Placenta pathology
Pre-Eclampsia pathology
Pregnancy
RNA, Messenger metabolism
Scavenger Receptors, Class E genetics
Uterine Neoplasms
Lipoproteins, LDL metabolism
NF-E2-Related Factor 2 metabolism
Placenta metabolism
Pre-Eclampsia metabolism
Scavenger Receptors, Class E metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1945-7197
- Volume :
- 97
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- The Journal of clinical endocrinology and metabolism
- Publication Type :
- Academic Journal
- Accession number :
- 22791762
- Full Text :
- https://doi.org/10.1210/jc.2012-1268