Document Detail


Reactive oxygen species controls endometriosis progression.
MedLine Citation:
PMID:  19498006     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Endometriosis is associated with chronic inflammation, and reactive oxygen species (ROS) are proinflammatory mediators that modulate cell proliferation. We have investigated whether the dysregulation of ROS production in endometriotic cells correlates with a pro-proliferative phenotype and can explain the spreading of this disease. Stromal and epithelial cells were purified from ovarian endometrioma and eutopic endometrium from 14 patients with endometriosis to produce four primary cell lines from each patient. ROS production, detoxification pathways, cell proliferation, and mitogen-activated protein kinase pathway activation were studied and compared with epithelial and stromal cell lines from 14 patients without endometriosis. Modulation of the proliferation of endometriosis by N-acetyl-cysteine, danazol, and mifepristone was tested in vitro and in 28 nude mice implanted with endometriotic tissue of human origin. Endometriotic cells displayed higher endogenous oxidative stress with an increase in ROS production, alterations in ROS detoxification pathways, and a drop in catalase levels, as observed for tumor cells. This increase in endogenous ROS correlated with increased cellular proliferation and activation of ERK1/2. These phenomena were abrogated by the antioxidant molecule N-acetyl-cysteine both in vitro and in a mouse model of endometriosis. Human endometriotic cells display activated pERK, enhanced ROS production, and proliferative capability. Our murine model shows that antioxidant molecules could be used as safe and efficient treatments for endometriosis.
Authors:
Charlotte Ngô; Christiane Chéreau; Carole Nicco; Bernard Weill; Charles Chapron; Frédéric Batteux
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-06-04
Journal Detail:
Title:  The American journal of pathology     Volume:  175     ISSN:  1525-2191     ISO Abbreviation:  Am. J. Pathol.     Publication Date:  2009 Jul 
Date Detail:
Created Date:  2009-06-26     Completed Date:  2009-07-15     Revised Date:  2010-09-27    
Medline Journal Info:
Nlm Unique ID:  0370502     Medline TA:  Am J Pathol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  225-34     Citation Subset:  AIM; IM    
Affiliation:
Faculté de Médecine, Service de Gynécologie Obstétrique II et Médecine de la Reproduction, AP-HP Hôpital Cochin, Paris, France.
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MeSH Terms
Descriptor/Qualifier:
Adult
Animals
Antioxidants / pharmacology
Blotting, Western
Catalase / drug effects,  metabolism
Cell Line
Cell Proliferation / drug effects
Disease Progression
Endometriosis / metabolism*
Extracellular Signal-Regulated MAP Kinases / drug effects,  metabolism
Female
Humans
Hydrogen Peroxide / metabolism
Mice
Mice, Nude
Oxidative Stress / physiology*
Reactive Oxygen Species / metabolism*
Superoxide Dismutase / drug effects,  metabolism
Chemical
Reg. No./Substance:
0/Antioxidants; 0/Reactive Oxygen Species; 7722-84-1/Hydrogen Peroxide; EC 1.11.1.6/Catalase; EC 1.15.1.1/Superoxide Dismutase; EC 2.7.11.24/Extracellular Signal-Regulated MAP Kinases
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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