Document Detail

High dosing of α-tocopherol inhibits rat liver regeneration by modifying signal transducer and activator of transcription protein expression and its correlation with cell redox state and retinoid metabolism.
MedLine Citation:
PMID:  22826360     Owner:  NLM     Status:  MEDLINE    
Lipid peroxidation (LP) promoted by partial hepatectomy (PH) is qualitatively distinct among subcellular fractions and temporally transient, probably being a necessary physiological event for rat liver regeneration. In fact, α-tocopherol (vitamin E [VE]) exerts adverse effects, partially inhibiting PH-induced rat liver regeneration and inducing decreased cyclin D1 expression. The phosphorylation of signal transducer and activator of transcription (STAT) factors 1 and 3 are involved in DNA synthesis and cyclin D1 expression after PH, which is stimulated by production of retinoic acid (RA). Hence, this study was aimed at addressing these events, and its association with cell redox state and oxidative stress, probably underlying VE effects on rat liver regeneration. PH-enhanced activation of STAT proteins, mainly as activated STAT-3, significantly change the cytoplasmic pool for STATs. The latter was associated to a more reduced cytoplasmic redox state and increased alcohol dehydrogenase (ADH)-mediated retinol oxidation to RA. Whereas α-tocopherol promoted minor changes in the parameters tested when administered to sham (control)-animals, pretreatment with VE blocked the PH-induced increase of reactive oxygen species (ROS), altering the pattern of STAT protein activation, blunting RA formation by decreased ADH activity, inducing higher liver caspase-3 activity and increasing tumor necrosis factor-α concentrations, while levels of interleukin-6 were decreased; altogether coinciding with disturbed PH-promoted changes on the liver redox state. In conclusion, altered activation and translocation of STAT-1 and -3 proteins and inhibited retinoid metabolism seem to be involved in the VE-induced inhibition of rat liver regeneration. Data suggest that a PH-induced increase of ROS could participate in the activation of STAT factors, retinoid metabolism and changes in the cell redox state during proliferation of liver cells.
Lourdes Sánchez-Sevilla; Edgar Mendieta-Condado; Rolando Hernández-Muñoz
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-07-23
Journal Detail:
Title:  Experimental biology and medicine (Maywood, N.J.)     Volume:  237     ISSN:  1535-3699     ISO Abbreviation:  Exp. Biol. Med. (Maywood)     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-08-09     Completed Date:  2012-10-26     Revised Date:  2013-09-26    
Medline Journal Info:
Nlm Unique ID:  100973463     Medline TA:  Exp Biol Med (Maywood)     Country:  England    
Other Details:
Languages:  eng     Pagination:  811-21     Citation Subset:  IM    
Departamento de Biología Celular y Desarrollo, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Apdo. Postal 70-243, Ave. Universidad # 3000, Copilco, México 04510, D.F., Mexico.
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MeSH Terms
Blotting, Western
Caspases / metabolism
Chromatography, High Pressure Liquid
Cytosol / enzymology
Dose-Response Relationship, Drug
Interleukin-6 / biosynthesis,  blood,  metabolism
Liver Regeneration / drug effects*
Oxidative Stress
Rats, Wistar
Retinoids / metabolism*
STAT Transcription Factors / metabolism*
Tumor Necrosis Factor-alpha / biosynthesis,  blood,  metabolism
alpha-Tocopherol / administration & dosage,  pharmacology*
Reg. No./Substance:
0/Interleukin-6; 0/Retinoids; 0/STAT Transcription Factors; 0/Tumor Necrosis Factor-alpha; 59-02-9/alpha-Tocopherol; EC 3.4.22.-/Caspases

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

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