Allameh Abdolamir, Ahmadi-Ashtiani Hamidreza, Emami Aleagha Mohammad Sajad, Rastegar Hossein
Department of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
Cell Biochem Funct. 2014 Mar;32(2):194-200. doi: 10.1002/cbf.2994. Epub 2013 Sep 5.
Differentiation of mesenchymal stem cells (MSCs) to hepatocytes-like cells is associated with alteration in the level of reactive oxygen species (ROS) and antioxidant defense system. Here, we report the role of glutathione in the functions of hepatocytes derived from MSCs. The stem cells undergoing differentiation were treated with glutathione modifiers [buthionine sulfoxide (BSO) or N-acetyl cysteine (NAC)], and hepatocytes were collected on day 14 of differentiation and analysed for their biological and metabolic functions. Differentiation process has been performed in presence of glutathione modifiers viz. BSO and NAC. Depending on the level of cellular glutathione, the proliferation rate of MSCs was affected. Glutathione depletion by BSO resulted in increased levels of albumin and ROS in hepatocytes. Whereas, albumin and ROS were inhibited in cells treated with glutathione precursor (NAC). The metabolic function of hepatocytes was elevated in BSO-treated cells as judged by increased urea, transferrin, albumin, alanine transaminase and aspartate transaminase secretions in the media. However, the metabolic activity of the hepatocytes was inhibited when glutathione was increased by NAC. We conclude that the efficiency of metabolic function of hepatocytes is inversely related to the levels of cellular glutathione. These data may suggest a novel role of glutathione in regulation of metabolic function of hepatocytes.
间充质干细胞（MSCs）向肝细胞样细胞的分化与活性氧（ROS）水平和抗氧化防御系统的改变有关。在此，我们报告了谷胱甘肽在源自MSCs的肝细胞功能中的作用。用谷胱甘肽调节剂[丁硫氨酸亚砜（BSO）或N-乙酰半胱氨酸（NAC）]处理正在分化的干细胞，并在分化第14天收集肝细胞，分析其生物学和代谢功能。分化过程在谷胱甘肽调节剂即BSO和NAC存在的情况下进行。根据细胞内谷胱甘肽水平，MSCs的增殖率受到影响。BSO导致的谷胱甘肽耗竭导致肝细胞中白蛋白和ROS水平升高。而在用谷胱甘肽前体（NAC）处理的细胞中，白蛋白和ROS受到抑制。根据培养基中尿素、转铁蛋白、白蛋白、丙氨酸转氨酶和天冬氨酸转氨酶分泌增加判断，BSO处理的细胞中肝细胞的代谢功能增强。然而，当NAC使谷胱甘肽增加时，肝细胞的代谢活性受到抑制。我们得出结论，肝细胞代谢功能的效率与细胞内谷胱甘肽水平呈负相关。这些数据可能提示谷胱甘肽在调节肝细胞代谢功能方面具有新作用。
