Vicente C P, Fortuna V A, Margis R, Trugo L, Borojevic R
Departamento de Bioquímica, Insituto de Química, Universidade Federal do Rio de Janeiro, Brazil.
Mol Cell Biochem. 1998 Oct;187(1-2):11-21. doi: 10.1023/a:1006886308490.
Liver is a major site of retinoid metabolism and storage, and more than 80% of the liver retinoids are stored in hepatic stellate cells. These cells represent less than 1% of the total liver protein, reaching a very high relative intracellular retinoid concentration. The plasma level of retinol is maintained close to 2 microM, and hepatic stellate cells have to be able both to uptake or to release retinol depending upon the extracellular retinol status. In view of their paucity in the liver tissue, stellate cells have been studied in primary cultures, in which they loose rapidly the stored lipids and retinol, and convert spontaneously into the activated myofibroblast phenotype, turning a long-term study of their retinol metabolism impossible. We have analyzed the retinol metabolism in the established GRX cell line, representative of stellate cells. We showed that this cell line behaves very similarly, with respect the retinol uptake and release, to primary cultures of hepatic stellate cells. Moreover, we showed that the cellular retinol binding protein (CRBP-I) expression in these cells, relevant for both uptake and esterification of retinol, responds to the extracellular retinol status, and is correlated to the retinol binding capacity of the cytosol. Its expression is not associated with the overall induction of the lipocyte phenotype by other agents. We conclude that the GRX cell line represents an in vitro model of hepatic stellate cells, and responds very efficiently to wide variations of the extracellular retinol status by autonomous controls of its uptake, storage or release.
肝脏是视黄醇代谢和储存的主要场所，超过80%的肝脏视黄醇储存在肝星状细胞中。这些细胞占肝脏总蛋白的比例不到1%，细胞内视黄醇浓度相对较高。视黄醇的血浆水平维持在接近2微摩尔，肝星状细胞必须能够根据细胞外视黄醇状态摄取或释放视黄醇。鉴于它们在肝脏组织中数量稀少，已在原代培养中对星状细胞进行了研究，在原代培养中它们会迅速失去储存的脂质和视黄醇，并自发转化为活化的成肌纤维细胞表型，从而无法对其视黄醇代谢进行长期研究。我们分析了已建立的代表星状细胞的GRX细胞系中的视黄醇代谢。我们发现，该细胞系在视黄醇摄取和释放方面的行为与肝星状细胞原代培养非常相似。此外，我们发现这些细胞中与视黄醇摄取和酯化相关的细胞视黄醇结合蛋白（CRBP-I）表达会对细胞外视黄醇状态作出反应，并与细胞质的视黄醇结合能力相关。其表达与其他因子对脂肪细胞表型的总体诱导无关。我们得出结论，GRX细胞系代表肝星状细胞的体外模型，并且通过自主控制其摄取、储存或释放对视黄醇细胞外状态的广泛变化做出非常有效的反应。
