A tryptophan derivative, ITE, enhances liver cell metabolic functions in vitro.

A tryptophan derivative, ITE, enhances liver cell metabolic functions in vitro.
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DOI:
10.3892/ijmm.2016.2825
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发表时间:
2017-01
影响因子:
5.4
通讯作者:
Li L
Li L
中科院分区:
医学3区
文献类型:
--
作者:
Zhang X;Lu J;He B;Tang L;Liu X;Zhu D;Cao H;Wang Y;Li L

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细胞包封通过将分离的细胞并入微胶囊中来提供三维支持,目的是同时维持细胞存活和功能,以及为生物反应器提供与体内观察到的类似的体外主动转运。然而,微囊化细胞的生物转化和代谢功能在临床应用中并不令人满意。为此,在这项研究中,肝癌衍生的Huh 7细胞/C3 A细胞与2-(1′ H-吲哚-3 ′-羰基)-噻唑-4-羧酸甲酯(ITE),内源性无毒配体的芳烃受体,在单层培养和微球。测定mRNA和蛋白水平,以及药物代谢酶、白蛋白分泌和尿素合成的代谢活性。当Huh 7和C3 A细胞在二维表面上单层培养时,ITE提高了蛋白水平和主要细胞色素P450(CYP 450)酶CYP 1A 1,CYP 1A 2,CYP 3A 4和CYP 1B 1的代谢活性,并轻微增加了白蛋白分泌和尿素合成。此外,当在微球上培养时,ITE还显著增加了两种肝细胞系中CYP 1A 1、CYP 1A 2、CYP 3A 4和CYP 1B 1的蛋白水平和代谢活性。总体而言,我们的研究结果表明,ITE增强主要CYP 450酶的酶活性和单层或微球培养的肝细胞的代谢功能,表明它可以用于改善肝细胞的功能。因此,它可能在未来用于治疗肝脏疾病。
Cell encapsulation provides a three-dimensional support by incorporating isolated cells into microcapsules with the goal of simultaneously maintaining cell survival and function, as well as providing active transport for a bioreactor in vitro similarly to that observed in vivo. However, the biotransformation and metabolic functions of the encapsulated cells are not satisfactory for clinical applications. For this purpose, in this study, hepatoma-derived Huh7 cells/C3A cells were treated with 2-(1′H-indole-3′-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE), an endogenous non-toxic ligand for aryl hydrocarbon receptor, in monolayer cultures and on microspheres. The mRNA and protein levels, as well as the metabolic activities of drug metabolizing enzymes, albumin secretion and urea synthesis were determined. When the Huh7 and C3A cells cultured in a monolayer on two-dimensional surfaces, ITE enhanced the protein levels and the metabolic activities of the major cytochrome P450 (CYP450) enzymes, CYP1A1, CYP1A2, CYP3A4 and CYP1B1, and slightly increased albumin secretion and urea synthesis. Moreover, when cultured on microspheres, ITE also substantially increased the protein levels and metabolic activities of CYP1A1, CYP1A2, CYP3A4 and CYP1B1 in both liver cell lines. On the whole, our findings indicate that ITE enhances the enzymatic activities of major CYP450 enzymes and the metabolic functions of liver cells cultured in monolayer or on microspheres, indicating that it may be utilized to improve the functions of hepatocytes. Thus, it may be used in the future for the treatment of liver diseases.
色氨酸衍生物调节干细胞样癌细胞中 Oct4 的转录。
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