The cholesterol metabolite 25-hydroxycholesterol activates estrogen receptor α-mediated signaling in cancer cells and in cardiomyocytes.

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...

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Main Authors: Rosamaria Lappano, Anna Grazia Recchia, Ernestina Marianna De Francesco, Tommaso Angelone, Maria Carmela Cerra, Didier Picard, Marcello Maggiolini
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2011-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3031608?pdf=render
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author Rosamaria Lappano
Anna Grazia Recchia
Ernestina Marianna De Francesco
Tommaso Angelone
Maria Carmela Cerra
Didier Picard
Marcello Maggiolini
author_facet Rosamaria Lappano
Anna Grazia Recchia
Ernestina Marianna De Francesco
Tommaso Angelone
Maria Carmela Cerra
Didier Picard
Marcello Maggiolini
author_sort Rosamaria Lappano
collection DOAJ
description 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.
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spelling doaj.art-b04ba1ebf0b64bae8f3909f92d05e31d2022-12-22T00:13:23ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-01-0161e1663110.1371/journal.pone.0016631The cholesterol metabolite 25-hydroxycholesterol activates estrogen receptor α-mediated signaling in cancer cells and in cardiomyocytes.Rosamaria LappanoAnna Grazia RecchiaErnestina Marianna De FrancescoTommaso AngeloneMaria Carmela CerraDidier PicardMarcello MaggioliniThe 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.http://europepmc.org/articles/PMC3031608?pdf=render
spellingShingle Rosamaria Lappano
Anna Grazia Recchia
Ernestina Marianna De Francesco
Tommaso Angelone
Maria Carmela Cerra
Didier Picard
Marcello Maggiolini
The cholesterol metabolite 25-hydroxycholesterol activates estrogen receptor α-mediated signaling in cancer cells and in cardiomyocytes.
PLoS ONE
title The cholesterol metabolite 25-hydroxycholesterol activates estrogen receptor α-mediated signaling in cancer cells and in cardiomyocytes.
title_full The cholesterol metabolite 25-hydroxycholesterol activates estrogen receptor α-mediated signaling in cancer cells and in cardiomyocytes.
title_fullStr The cholesterol metabolite 25-hydroxycholesterol activates estrogen receptor α-mediated signaling in cancer cells and in cardiomyocytes.
title_full_unstemmed The cholesterol metabolite 25-hydroxycholesterol activates estrogen receptor α-mediated signaling in cancer cells and in cardiomyocytes.
title_short The cholesterol metabolite 25-hydroxycholesterol activates estrogen receptor α-mediated signaling in cancer cells and in cardiomyocytes.
title_sort cholesterol metabolite 25 hydroxycholesterol activates estrogen receptor α mediated signaling in cancer cells and in cardiomyocytes
url http://europepmc.org/articles/PMC3031608?pdf=render
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