Laboratory of Experimental Hepatology and Drug Targeting (HEVEFARM), National Institute for the Study of Liver and Gastrointestinal Diseases (CIBERehd), University of Salamanca, Salamanca, Spain.
Br J Nutr. 2011 Dec;106(12):1814-25. doi: 10.1017/S0007114511002273. Epub 2011 Jul 1.
Ascorbic acid uptake is a key step in determining the overall bioactivity of this vitamin. Expression of Na-dependent vitamin C transporters (SVCT; SLC23A1 and SLC23A2) during long-term oxidative stress occurring in several chronic liver diseases may determine the antioxidant defence in this organ. In patients with hepatocellular cholestasis, primary biliary cirrhosis, haemochromatosis and non-alcoholic steatohepatitis, using real-time RT-PCR, an enhanced hepatic expression of both SLC23A1 and SLC23A2, but not other organic anions transporters, such as OATP1A2, OATP1B1 and OATP1B3, was found. To further investigate these findings, we used secondary biliary cirrhosis induced in rats by long-term biliary obstruction as a model of chronic liver disease accompanied by oxidative stress because of bile acid accumulation. In control rat liver, expression of Slc23a1 was low at birth, increased progressively up to adulthood and decreased in senescence, whereas expression of Slc23a2 did not change significantly after birth. In 8-week-old rats, immunohistochemistry and confocal microscopy studies revealed the expression in hepatocytes and bile duct cells of mainly Slc23a1, whereas both Slc23a1 and Slc23a2 were expressed in endothelial, stellate and Kupffer cells. In adult rats, when obstructive cholestasis was maintained for 8 weeks, a significant up-regulation of Slc23a2 accompanied by a down-regulation of Slc23a1 was found. In sum, there is a selective cell-type distribution of SVCT in the liver tissue, which, in addition to differential control in the expression of both isoforms, may play a role in the ability of different liver cell types to take up vitamin C under physiological and pathological conditions.
抗坏血酸摄取是决定这种维生素整体生物活性的关键步骤。在几种慢性肝病中发生的长期氧化应激过程中，Na 依赖性维生素 C 转运体（SVCT；SLC23A1 和 SLC23A2）的表达可能决定了该器官的抗氧化防御能力。在肝细胞性胆汁淤积、原发性胆汁性肝硬化、血色病和非酒精性脂肪性肝炎患者中，通过实时 RT-PCR 发现，两种 SLC23A1 和 SLC23A2 的肝表达增强，但其他有机阴离子转运体（如 OATP1A2、OATP1B1 和 OATP1B3）的表达没有增强。为了进一步研究这些发现，我们使用长期胆道阻塞诱导的大鼠次级胆汁性肝硬化作为伴有胆汁酸积聚的慢性肝病合并氧化应激的模型。在对照大鼠肝脏中，Slc23a1 的表达在出生时较低，在成年期逐渐增加，在衰老时降低，而 Slc23a2 的表达在出生后没有明显变化。在 8 周龄大鼠中，免疫组织化学和共聚焦显微镜研究显示 Slc23a1 主要在肝细胞和胆管细胞中表达，而 Slc23a1 和 Slc23a2 均在内皮细胞、星状细胞和库普弗细胞中表达。在成年大鼠中，当阻塞性胆汁淤积持续 8 周时，发现 Slc23a2 的表达显著上调，而 Slc23a1 的表达下调。总之，SVCT 在肝组织中有选择性的细胞类型分布，除了两种同工型表达的差异调控外，还可能在不同肝细胞类型在生理和病理条件下摄取维生素 C 的能力中发挥作用。
