Lee Seungwoo, Kim Soohee, Hwang Seungwoo, Cherrington Nathan J, Ryu Doug-Young
BK21 Plus Program for Creative Veterinary Science Research, Research Institute for Veterinary Science and College of Veterinary Medicine, Seoul National University, Gwanak-gu, Seoul 08826, Republic of Korea.
Korean Bioinformation Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141, Republic of Korea.
Oncotarget. 2017 Jun 28;8(38):63370-63381. doi: 10.18632/oncotarget.18812. eCollection 2017 Sep 8.
Nonalcoholic fatty liver disease (NAFLD) is categorized into nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH) and has emerged as a risk factor for more critical clinical conditions. However, the underlying mechanisms of NAFLD pathogenesis are not fully understood. In this study, expression of proteins associated with endoplasmic reticulum (ER) stress, apoptosis and autophagy were analyzed in normal, NAFL and NASH human livers by western blotting. Levels of some ER stress-transducing transcription factors, including cleaved activating transcription factor 6, were higher in NASH than in the normal tissues. However, the expression of a majority of the ER chaperones and foldases analyzed, including glucose-regulated protein 78 and ER protein 44, was lower in NASH than in the normal tissues. Levels of apoptosis markers, such as cleaved poly (ADP-ribose) polymerase, were also lower in NASH tissues, in which expression of some B-cell lymphoma-2 family proteins was up- or down-regulated compared to the normal tissues. The level of the autophagy substrate p62 was not different in NASH and normal tissues, although some autophagy regulators were up- or down-regulated in the NASH tissues compared to the normal tissues. Levels of most of the proteins analyzed in NAFL tissues were either similar to those in one of the other two types, NASH and normal, or were somewhere in between. Together, these findings suggest that regulation of certain important tissues processes involved in protein quality control and cell survival were broadly compromised in the NAFLD tissues.
非酒精性脂肪性肝病（NAFLD）分为非酒精性脂肪肝（NAFL）和非酒精性脂肪性肝炎（NASH），并已成为更严重临床病症的一个危险因素。然而，NAFLD发病机制的潜在机制尚未完全明确。在本研究中，通过蛋白质印迹法分析了正常、NAFL和NASH人肝脏中与内质网（ER）应激、凋亡和自噬相关的蛋白质表达。包括裂解激活转录因子6在内的一些ER应激转导转录因子的水平在NASH中高于正常组织。然而，所分析的大多数ER伴侣蛋白和折叠酶的表达，包括葡萄糖调节蛋白78和ER蛋白44，在NASH中低于正常组织。凋亡标志物的水平，如裂解的聚（ADP - 核糖）聚合酶，在NASH组织中也较低，其中一些B细胞淋巴瘤 - 2家族蛋白的表达与正常组织相比上调或下调。自噬底物p62的水平在NASH和正常组织中没有差异，尽管与正常组织相比，一些自噬调节因子在NASH组织中上调或下调。在NAFL组织中分析的大多数蛋白质水平要么与NASH和正常组织中的一种相似，要么介于两者之间。总之，这些发现表明，NAFLD组织中参与蛋白质质量控制和细胞存活的某些重要组织过程的调节受到广泛损害。
