Information de reference pour ce titreAccession Number: | 00002401-201208020-00002.
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Author: | Lin, Jianguo 1; Tang, Youcai 1; Kang, Qiaohua 1; Feng, Yunfeng 2; Chen, Anping 1
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Institution: | (1) Department of Pathology, School of Medicine, Saint Louis University, St. Louis, MO, USA (2) Department of Medicine, Washington University, St. Louis, MO, USA
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Title: | |
Source: | British Journal of Pharmacology. 166(8):2212-2227, August 2012.
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Abstract: | BACKGROUND AND PURPOSE: Diabetes is characterized by hyperglycaemia, which facilitates the formation of advanced glycation end-products (AGEs). Type 2 diabetes mellitus is commonly accompanied by non-alcoholic steatohepatitis, which could lead to hepatic fibrosis. Receptor for AGEs (RAGE) mediates effects of AGEs and is associated with increased oxidative stress, cell growth and inflammation. The phytochemical curcumin inhibits the activation of hepatic stellate cells (HSCs), the major effectors during hepatic fibrogenesis. The aim of this study was to explore the underlying mechanisms of curcumin in the elimination of the stimulating effects of AGEs on the activation of HSCs. We hypothesize that curcumin eliminates the effects of AGEs by suppressing gene expression of RAGE.
EXPERIMENTAL APPROACH: Gene promoter activities were evaluated by transient transfection assays. The expression of rage was silenced by short hairpin RNA. Gene expression was analysed by real-time PCR and Western blots. Oxidative stress was evaluated.
KEY RESULTS: AGEs induced rage expression in cultured HSCs, which played a critical role in the AGEs-induced activation of HSCs. Curcumin at 20 [mu]M eliminated the AGE effects, which required the activation of PPAR[gamma]. In addition, curcumin attenuated AGEs-induced oxidative stress in HSCs by elevating the activity of glutamate-cysteine ligase and by stimulating de novo synthesis of glutathione, leading to the suppression of gene expression of RAGE.
CONCLUSION AND IMPLICATIONS: Curcumin suppressed gene expression of RAGE by elevating the activity of PPAR[gamma] and attenuating oxidative stress, leading to the elimination of the AGE effects on the activation of HSCs.
LINKED ARTICLE: This article is commented on by Stefanska, pp. 2209-2211 of this issue. To view this commentary visit http://dx.doi.org/10.1111/j.1476...- ouverture dans une nouvelle fenêtre
Copyright (C) 2012 John Wiley & Sons, Inc.
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Author Keywords: | diabetes; hyperglycaemia; hepatic fibrosis; hepatic stellate cells; gene expression; phytochemical.
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Language: | English.
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Document Type: | RESEARCH PAPER: RESEARCH PAPERS WITH COMMENTARIES.
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Journal Subset: | Behavioral & Social Sciences.
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ISSN: | 0007-1188
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NLM Journal Code: | b00, 7502536
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DOI Number: | https://dx.doi.org/10.1111/j.147...- ouverture dans une nouvelle fenêtre
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