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  • 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.

PloS one (2011-02-10)
Rosamaria Lappano, Anna Grazia Recchia, Ernestina Marianna De Francesco, Tommaso Angelone, Maria Carmela Cerra, Didier Picard, Marcello Maggiolini
ABSTRACT

The hydroxylated derivatives of cholesterol, such as the oxysterols, play important roles in lipid metabolism. In particular, 25-hydroxycholesterol (25 HC) has been implicated in a variety of metabolic events including cholesterol homeostasis and atherosclerosis. 25 HC 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 25 HC, have been found to be elevated in hypercholesterolemic serum. Here, we demonstrate that the estrogen receptor (ER) α mediates gene expression changes and growth responses induced by 25 HC in breast and ovarian cancer cells. Moreover, 25 HC exhibits the ERα-dependent ability like 17 β-estradiol (E2) to inhibit the up-regulation of HIF-1α and connective tissue growth factor by hypoxic conditions in cardiomyocytes and rat heart preparations and to prevent the hypoxia-induced apoptosis. The estrogen action exerted by 25 HC may be considered as an additional factor involved in the progression of breast and ovarian tumors. Moreover, the estrogen-like activity of 25 HC elicited in the cardiovascular system may play a role against hypoxic environments.

MATERIALS
Product Number
Brand
Product Description

Avanti
25-hydroxycholesterol (D6), Avanti Research - A Croda Brand
Sigma-Aldrich
β-Estradiol, ≥98%
Avanti
Sphingosine (d17:1), Avanti Research - A Croda Brand LM2000, ethanol solution