Department of Experimental and Clinical Pharmacology, Pomeranian Medical University, 70-111 Szczecin, Poland.
Department of General and Transplantation Surgery, County Hospital, 71-455 Szczecin, Poland.
Int J Mol Sci. 2020 Feb 26;21(5):1606. doi: 10.3390/ijms21051606.
Membrane monocarboxylate transporter 1 (/MCT1) plays an important role in hepatocyte homeostasis, as well as drug handling. However, there is no available information about the impact of liver pathology on the transporter levels and function. The study was aimed to quantify mRNA (qRT-PCR) and MCT1 protein abundance (liquid chromatography-tandem mass spectrometry (LC---MS/MS)) in the livers of patients diagnosed, according to the standard clinical criteria, with hepatitis C, primary biliary cirrhosis, primary sclerosing hepatitis, alcoholic liver disease (ALD), and autoimmune hepatitis. The stage of liver dysfunction was classified according to Child-Pugh score. Downregulation of /MCT1 levels was observed in all liver pathology states, significantly for ALD. The progression of liver dysfunction, from Child-Pugh class A to C, involved the gradual decline in mRNA and MCT1 protein abundance, reaching a clinically significant decrease in class C livers. Reduced levels of MCT1 were associated with significant intracellular lactate accumulation. The MCT1 transcript and protein did not demonstrate significant correlations regardless of the liver pathology analyzed, as well as the disease stage, suggesting posttranscriptional regulation, and several microRNAs were found as potential regulators of MCT1 abundance. MCT1 membrane immunolocalization without cytoplasmic retention was observed in all studied liver pathologies. Overall, the study demonstrates that /MCT1 is involved in liver pathology, especially in ALD.
单羧酸转运蛋白 1（/MCT1）在肝细胞稳态以及药物处理中发挥着重要作用。然而，目前尚无关于肝病理对转运体水平和功能影响的信息。本研究旨在根据标准临床标准，定量检测丙型肝炎、原发性胆汁性肝硬化、原发性硬化性胆管炎、酒精性肝病（ALD）和自身免疫性肝炎患者肝脏中 MCT1 的 mRNA（qRT-PCR）和蛋白丰度（液相色谱-串联质谱法（LC-MS/MS））。根据Child-Pugh 评分对肝功能障碍的阶段进行分类。在所有肝脏病理状态下均观察到/MCT1 水平下调，ALD 尤为显著。随着肝功能障碍的进展，从 Child-Pugh 分级 A 到 C，MCT1 mRNA 和蛋白丰度逐渐下降，C 级肝脏中达到临床显著下降。MCT1 水平降低与细胞内乳酸积累显著相关。MCT1 转录本和蛋白之间无论在分析的肝脏病理还是疾病阶段均无显著相关性，提示存在转录后调控，并且发现了几种 microRNAs 作为 MCT1 丰度的潜在调节剂。在所有研究的肝脏病理中均观察到 MCT1 膜免疫定位而无细胞质滞留。总体而言，本研究表明/MCT1 参与了肝脏病理，尤其是 ALD。
