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The role of cellular prion protein in lipid metabolism in the liver.
Prion ( IF 1.9 ) Pub Date : 2020-12-01 , DOI: 10.1080/19336896.2020.1729074
Amandeep Singh Arora 1 , Saima Zafar 1 , Umair Latif 2 , Franc Llorens 1, 3 , Mihm Sabine 2 , Prateek Kumar 1 , Waqas Tahir 1 , Katrin Thüne 1 , Mohsin Shafiq 1 , Matthias Schmitz 1 , Inga Zerr 1
Affiliation  

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.

中文翻译:

细胞朊病毒蛋白在肝脏脂质代谢中的作用。

细胞朊病毒蛋白 (PrPC) 是一种质膜糖磷脂酰肌醇锚定蛋白,它参与多种功能,包括神经保护和氧化应激。迄今为止,大部分 PrPC 功能研究是在神经元组织或细胞系中完成的;PrPC 在非神经组织如肝脏中的作用知之甚少。为了表征 PrPC 在肝脏中的作用,在 PrPC 敲除小鼠的肝组织中应用了蛋白质组学方法。蛋白质组分析和生化验证表明,PrPC 基因敲除小鼠肝脏脂肪堆积过多,与脂质代谢相关基因的 mRNA 表达发生变化。此外,较高的 Bax 与 Bcl2 比率,上调 PrPC 敲除小鼠肝脏中 tgfb1 mRNA 的表达,进一步显示了代谢疾病的证据。PrPC 在脂肪酸处理的 AML12 肝细胞系中的过度表达导致细胞内过多脂肪积累的减少;显示了 PrPC 水平和脂质代谢的关联。因此,基于对衰老 PrPC 敲除小鼠肝脏中过多脂肪球的观察以及 PrPC 过表达的 AML12 细胞系中脂肪积累的减少,描述了 PrPC 在脂质代谢中的作用。
更新日期:2020-05-06
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