Guimarães E L M, Franceschi M F S, Grivicich I, Dal-Pizzol F, Moreira J C F, Guaragna R M, Borojevic R, Margis R, Guma F C R
Departamento de Bioquímica, ICBS, UFRGS. Porto Alegre, RS, Brazil.
Liver Int. 2006 May;26(4):477-85. doi: 10.1111/j.1478-3231.2006.01245.x.
BACKGROUND/AIMS: Oxidative stress plays an important role in liver fibrosis. Under pathological conditions, hepatic stellate cells (HSC) undergo an activation process, developing a myofibroblast-like phenotype from the lipocyte phenotype. In this study, we determined the levels of oxidative stress and proliferation in different activation states of an experimental model of mouse HSC, the GRX cell line. These cells can be induced in vitro to display a more activated state or a quiescent phenotype.
METHODS/RESULTS: We observed increased oxidative damage and higher levels of reactive oxygen species, measured by thiobarbituric acid reactive species and 2',7'-dichlorofluorescein diacetate, respectively, and diminished catalase activity in activated cells. Activation decreased proliferation and increased the number of cells in G2/M. Antioxidants N-acetylcysteine and Trolox varied in their capacity to correct the oxidative stress and proliferation status.
The differences in physiological functions of stellate cell phenotypes suggest a relationship between oxidative stress levels and activation state.
背景/目的:氧化应激在肝纤维化中起重要作用。在病理条件下,肝星状细胞(HSC)经历激活过程,从脂肪细胞表型转变为肌成纤维细胞样表型。在本研究中,我们测定了小鼠HSC实验模型GRX细胞系不同激活状态下的氧化应激水平和增殖情况。这些细胞可在体外被诱导呈现更激活的状态或静止表型。
方法/结果:我们观察到,通过硫代巴比妥酸反应性物质和二氯荧光素二乙酸酯分别测定,激活的细胞中氧化损伤增加、活性氧水平升高,而过氧化氢酶活性降低。激活降低了增殖并增加了处于G2/M期的细胞数量。抗氧化剂N-乙酰半胱氨酸和曲洛昔芬在纠正氧化应激和增殖状态的能力上存在差异。
星状细胞表型生理功能的差异表明氧化应激水平与激活状态之间存在关联。