Department of Neurology, Clinical Dementia Center, University Medical Center Göttingen and German Center for Neurodegenerative Diseases (DZNE), Göttingen, Germany.
Departments of Gastroenterology Endocrinology, University Medical Center Göttingen, Göttingen, Germany.
Prion. 2020 Dec;14(1):95-108. doi: 10.1080/19336896.2020.1729074.
Cellular prion protein (PrPC) is a plasma membrane glycophosphatidylinositol-anchored protein and it is involved in multiple functions, including neuroprotection and oxidative stress. So far, most of the PrPC functional research is done in neuronal tissue or cell lines; the role of PrPC in non-neuronal tissues such as liver is only poorly understood. To characterize the role of PrPC in the liver, a proteomics approach was applied in the liver tissue of PrPC knockout mice. The proteome analysis and biochemical validations showed an excessive fat accumulation in the liver of PrPC knockout mice with a change in mRNA expression of genes linked to lipid metabolism. In addition, the higher Bax to Bcl2 ratio, up-regulation of tgfb1 mRNA expression in PrPC knockout mice liver, further showed the evidences of metabolic disease. Over-expression of PrPC in fatty acid-treated AML12 hepatic cell line caused a reduction in excessive intracellular fat accumulation; shows association of PrPC levels and lipid metabolism. Therefore, based on observation of excessive fat globules in the liver of ageing PrPC knockout mice and the reduction of fat accumulation in AML12 cell line with PrPC over-expression, the role of PrPC in lipid metabolism is described.
细胞朊蛋白（PrPC）是一种质膜糖磷脂酰肌醇锚定蛋白，参与多种功能，包括神经保护和氧化应激。到目前为止，大多数 PrPC 功能研究都是在神经元组织或细胞系中进行的；PrPC 在肝脏等非神经组织中的作用知之甚少。为了研究 PrPC 在肝脏中的作用，采用蛋白质组学方法研究 PrPC 敲除小鼠的肝脏组织。蛋白质组分析和生化验证表明，PrPC 敲除小鼠肝脏中脂肪过度积累，与脂质代谢相关的基因的 mRNA 表达发生变化。此外，PrPC 敲除小鼠肝脏中 Bax 与 Bcl2 比值升高，tgfb1 mRNA 表达上调，进一步表明存在代谢疾病的证据。脂肪酸处理的 AML12 肝细胞系中 PrPC 的过表达导致细胞内过量脂肪积累减少；表明 PrPC 水平与脂质代谢有关。因此，基于观察到衰老的 PrPC 敲除小鼠肝脏中存在大量脂肪球，以及 AML12 细胞系中 PrPC 过表达可减少脂肪积累，描述了 PrPC 在脂质代谢中的作用。
