Document Detail


Opposing effects of oestradiol and progesterone on intracellular pathways and activation processes in the oxidative stress induced activation of cultured rat hepatic stellate cells.
MedLine Citation:
PMID:  16284289     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Oxidative stress, including the generation of reactive oxygen species (ROS), is involved in hepatofibrogenesis. The authors' previous studies have shown that oestradiol suppresses hepatic fibrosis in animal models and attenuates the activation of cultured rat hepatic stellate cells (HSCs), which possess oestrogen receptor subtype beta and are also activated by ROS.
AIMS: To define the mechanisms by which female sex hormones play an antifibrogenic role in activated HSCs, the effects of oestradiol and progesterone on ROS generation processes and intracellular pathways, leading to the activation of HSCs undergoing oxidative stress, was examined.
METHODS: HSCs, isolated from rats, were cultured for 7 days with oestradiol or progesterone for 24 hours as pretreatment, and oxidative stress was then induced by exposure to low doses of hydrogen peroxide for another 24 hours.
RESULTS: Oestradiol inhibited ROS generation and antioxidant enzyme loss via the suppression of NADH/NADPH oxidase activity, and attenuated hydrogen peroxide induced transforming growth factor-beta1 (TGF-beta1) expression, HSC proliferation and transformation, and the activation of mitogen activated protein kinase (MAPK) pathways and transcription factors. Progesterone exerted a stimulatory effect through the progesterone receptor on the induction of ROS generation processes and intracellular pathways, resulting in TGF-beta1 expression and HSC activation, and fibrogenic effects were inhibited by oestradiol.
CONCLUSION: These findings show for the first time that oestradiol inhibits the activation of transcription factors by suppressing ROS generation processes and the MAPK pathways, and inactivates the downstream transcription processes involved in TGF-beta1 expression and HSC activation, whereas progesterone acts in opposition to the favourable effects of oestradiol and its effects are blocked by oestradiol.
Authors:
T Itagaki; I Shimizu; X Cheng; Y Yuan; A Oshio; K Tamaki; H Fukuno; H Honda; Y Okamura; S Ito
Related Documents :
9400019 - In vitro pharmacological characterization of pd 166285, a new nanomolar potent and broa...
8443409 - Phosphorylation sites at the c-terminus of the platelet-derived growth factor receptor ...
17989109 - Role of endogenous opioids in modulating hsc activity in vitro and liver fibrosis in vivo.
12070119 - Adipocyte-derived plasma protein adiponectin acts as a platelet-derived growth factor-b...
21874259 - Phosphorylation and stabilization of c-myc by nemo renders cells resistant to ionizing ...
15474029 - Endothelin-1 is an essential co-factor for beta2-adrenergic receptor-induced proliferat...
23256519 - The way wnt works: components and mechanism.
16754879 - Activity of dual src-abl inhibitors highlights the role of bcr/abl kinase dynamics in d...
23732709 - Acid ceramidase induces sphingosine kinase 1/s1p receptor 2-mediated activation of onco...
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Gut     Volume:  54     ISSN:  0017-5749     ISO Abbreviation:  Gut     Publication Date:  2005 Dec 
Date Detail:
Created Date:  2005-11-14     Completed Date:  2005-12-12     Revised Date:  2013-06-07    
Medline Journal Info:
Nlm Unique ID:  2985108R     Medline TA:  Gut     Country:  England    
Other Details:
Languages:  eng     Pagination:  1782-9     Citation Subset:  AIM; IM    
Affiliation:
Department of Digestive and Cardiovascular Medicine, Tokushima University Graduate School, Kuramoto-cho, Tokushima 770-8503, Japan.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Animals
Cell Proliferation
Cells, Cultured
Enzyme-Linked Immunosorbent Assay
Estradiol / pharmacology*
Female
Gene Expression Regulation / drug effects
Hydrogen Peroxide / pharmacology
Lipid Peroxidation / drug effects
Liver / cytology,  drug effects*,  metabolism
Male
Mitogen-Activated Protein Kinases / metabolism
Multienzyme Complexes / metabolism
NAD / metabolism
NADH, NADPH Oxidoreductases / metabolism
Oxidative Stress / drug effects,  physiology
Progesterone / pharmacology*
Rats
Rats, Wistar
Reactive Oxygen Species / metabolism
Receptors, Progesterone / genetics,  metabolism
Reverse Transcriptase Polymerase Chain Reaction / methods
Signal Transduction / drug effects
Transforming Growth Factor beta / metabolism
Transforming Growth Factor beta1
Chemical
Reg. No./Substance:
0/Multienzyme Complexes; 0/Reactive Oxygen Species; 0/Receptors, Progesterone; 0/Tgfb1 protein, rat; 0/Transforming Growth Factor beta; 0/Transforming Growth Factor beta1; 50-28-2/Estradiol; 53-84-9/NAD; 57-83-0/Progesterone; 7722-84-1/Hydrogen Peroxide; EC 1.6.-/NADH oxidase; EC 1.6.-/NADH, NADPH Oxidoreductases; EC 2.7.11.24/Mitogen-Activated Protein Kinases
Comments/Corrections
Erratum In:
Gut. 2008 Nov;57(11):1634

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


Previous Document:  Anti-monocyte chemoattractant protein 1 gene therapy attenuates experimental chronic pancreatitis in...
Next Document:  Mechanism of action of a novel human ether-a-go-go-related gene channel activator.