Effect of asymmetric dimethylarginine on the activation of hepatic stellate cells and its mechanism / 中南大学学报(医学版)
Journal of Central South University(Medical Sciences)
; (12): 427-432, 2007.
Article
em Zh
| WPRIM
| ID: wpr-813867
Biblioteca responsável:
WPRO
ABSTRACT
OBJECTIVE@#To investigate the effect of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, on the activation of hepatic stellate cells (HSCs) and its mechanism.@*METHODS@#Primary HSCs isolated from SD rats were cultured and treated with different concentrations (1, 3 or 10micromol/L) of ADMA for various periods (12 approximately 48h). Expression of alpha-smooth muscle actin (alpha-SMA) and synthesis of type-I collagens in HSC were determined. Messenger RNA levels of the transforming growth factor-beta1 (TGF-beta(1)) in the HSCs were determined using RT-PCR. Intracellular reactive oxidant species (ROS) production was measured using oxidant-sensitive fluorescent indicator. Activation of nuclear factor-kappaB (NF-kappaB) was detected by electrophoretic mobility shift assay (EMSA).@*RESULTS@#ADMA could increase alpha-SMA-positive cells ratio and Type I collagens production of HSCs in a concentration- and time-dependent manner, concomitant with the increase of the TGF-beta(1) mRNA level. Treatment with ADMA (10micromol/L) significantly increased the intracellular ROS production and activated NF-kappaB. Such effects of ADMA on the level of TGF-beta(1) mRNA could be markedly attenuated by pretreatment with antioxidant pyrrolidine dithiocarbamate (25micromol/L).@*CONCLUSION@#ADMA can induce the HSC activation by increasing TGF-beta(1) expression through ROS-NF-kappaB-dependent pathway. Therefore, ADMA should be a novel and endogenous activator of HSC, which may be involved in the development of liver fibrosis.
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Base de dados:
WPRIM
Assunto principal:
Farmacologia
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Arginina
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RNA Mensageiro
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Expressão Gênica
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Células Cultivadas
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NF-kappa B
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Fator de Crescimento Transformador beta
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Actinas
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Espécies Reativas de Oxigênio
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Ratos Sprague-Dawley
Limite:
Animals
Idioma:
Zh
Revista:
Journal of Central South University(Medical Sciences)
Ano de publicação:
2007
Tipo de documento:
Article