Zheng Ze, Zhang Chunbin, Zhang Kezhong
The Center for Molecular Medicine and Genetics, The Wayne State University School of Medicine, Detroit, Michigan, USA.
Methods Enzymol. 2011;489:329-48. doi: 10.1016/B978-0-12-385116-1.00019-4.
In eukaryotic cells, the endoplasmic reticulum (ER) is the organelle that is responsible for protein folding and assembly, lipid and sterol biosynthesis, and intracellular calcium storage. Biochemical or pathophysiological stimuli that disrupt protein-folding reaction or increase protein-folding load can cause accumulation of unfolded or misfolded proteins in the ER lumen, a condition called "ER stress". As an adaptive intracellular stress response initiated from the ER, unfolded protein response (UPR) alleviates the accumulation of unfolded or misfolded proteins in the ER. It has been demonstrated that the UPR is a fundamental intracellular signal transduction response that is critical for health and disease. ER stress and other cellular stress responses, such as inflammation and oxidative stress, are integrated in many pathophysiological processes. Particularly, recent research demonstrated that ER stress and the UPR signaling are critically involved in the initiation and progression of nonalcoholic fatty liver disease (NAFLD). Under metabolic stress conditions, the UPR regulates transcriptional and translational programs that are associated with hepatic steatosis and inflammation, the major characteristics of NAFLD. In this chapter, we summarize reliable methods to quantitatively analyze the UPR and hepatic inflammation in the mouse model of NAFLD.
在真核细胞中，内质网（ER）是负责蛋白质折叠与组装、脂质和固醇生物合成以及细胞内钙储存的细胞器。破坏蛋白质折叠反应或增加蛋白质折叠负荷的生化或病理生理刺激可导致内质网腔中未折叠或错误折叠蛋白质的积累，这种情况称为“内质网应激”。作为从内质网引发的一种适应性细胞内应激反应，未折叠蛋白反应（UPR）可减轻内质网中未折叠或错误折叠蛋白质的积累。已证明，UPR是一种对健康和疾病至关重要的基本细胞内信号转导反应。内质网应激和其他细胞应激反应，如炎症和氧化应激，在许多病理生理过程中相互整合。特别是，最近的研究表明，内质网应激和UPR信号通路在非酒精性脂肪性肝病（NAFLD）的发生和发展中起关键作用。在代谢应激条件下，UPR调节与肝脂肪变性和炎症相关的转录和翻译程序，而肝脂肪变性和炎症是非酒精性脂肪性肝病的主要特征。在本章中，我们总结了在非酒精性脂肪性肝病小鼠模型中定量分析UPR和肝脏炎症的可靠方法。
