The Cholesterol Metabolite 25-Hydroxycholesterol Activates Estrogen Receptor α-Mediated Signaling in Cancer Cells and in Cardiomyocytes
The Cholesterol Metabolite 25-Hydroxycholesterol Activates Estrogen Receptor α-Mediated Signaling in Cancer Cells and in Cardiomyocytes
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DOI：
10.1371/journal.pone.0016631
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发表时间：
2011-01-31
期刊：
影响因子：
3.7
通讯作者：
Maggiolini, Marcello
中科院分区：
文献类型：
--
作者：
Lappano, Rosamaria;Recchia, Anna Grazia;Maggiolini, Marcello
Background: The hydroxylated derivatives of cholesterol, such as the oxysterols, play important roles in lipid metabolism. In particular, 25-hydroxycholesterol (25HC) has been implicated in a variety of metabolic events including cholesterol homeostasis and atherosclerosis. 25HC is detectable in human plasma after ingestion of a meal rich in oxysterols and following a dietary cholesterol challenge. In addition, the levels of oxysterols, including 25HC, have been found to be elevated in hypercholesterolemic serum.Methodology/Principal Findings: Here, we demonstrate that the estrogen receptor (ER) alpha mediates gene expression changes and growth responses induced by 25HC in breast and ovarian cancer cells. Moreover, 25HC exhibits the ER alpha-dependent ability like 17 beta-estradiol (E2) to inhibit the up-regulation of HIF-1 alpha and connective tissue growth factor by hypoxic conditions in cardiomyocytes and rat heart preparations and to prevent the hypoxia-induced apoptosis.Conclusions/Significance: The estrogen action exerted by 25HC may be considered as an additional factor involved in the progression of breast and ovarian tumors. Moreover, the estrogen-like activity of 25HC elicited in the cardiovascular system may play a role against hypoxic environments.
