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永生化人肝细胞(IHH)细胞系中的过氧化物酶体异常。

Peroxisomal abnormalities in the immortalized human hepatocyte (IHH) cell line.

作者信息

Klouwer Femke C C, Koster Janet, Ferdinandusse Sacha, Waterham Hans R

机构信息

Laboratory Genetic Metabolic Diseases, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.

Department of Pediatric Neurology, Emma Children's Hospital, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.

出版信息

Histochem Cell Biol. 2017 Apr;147(4):537-541. doi: 10.1007/s00418-016-1532-6. Epub 2016 Dec 24.

DOI:10.1007/s00418-016-1532-6
PMID:28013369
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5359384/
Abstract

The immortalized human hepatocyte (IHH) cell line is increasingly used for studies related to liver metabolism, including hepatic glucose, lipid, lipoprotein and triglyceride metabolism, and the effect of therapeutic interventions. To determine whether the IHH cell line is a good model to investigate hepatic peroxisomal metabolism, we measured several peroxisomal parameters in IHH cells and, for comparison, HepG2 cells and primary skin fibroblasts. This revealed a marked plasmalogen deficiency and a deficient fatty acid α-oxidation in the IHH cells, due to a defect of PEX7, a cytosolic receptor protein required for peroxisomal import of a subset of peroxisomal proteins. These abnormalities have consequences for the lipid homeostasis of these cells and thus should be taken into account for the interpretation of data previously generated by using this cell line and when considering using this cell line for future research.

摘要

永生化人肝细胞(IHH)细胞系越来越多地用于与肝脏代谢相关的研究,包括肝脏葡萄糖、脂质、脂蛋白和甘油三酯代谢以及治疗干预的效果。为了确定IHH细胞系是否是研究肝脏过氧化物酶体代谢的良好模型,我们测量了IHH细胞中的几个过氧化物酶体参数,并与HepG2细胞和原代表皮成纤维细胞进行比较。这揭示了IHH细胞中明显的缩醛磷脂缺乏和脂肪酸α-氧化缺陷,这是由于PEX7缺陷所致,PEX7是一种胞质受体蛋白,是过氧化物酶体中一部分过氧化物酶体蛋白导入所必需的。这些异常对这些细胞的脂质稳态有影响,因此在解释以前使用该细胞系产生的数据以及考虑将该细胞系用于未来研究时应予以考虑。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e4f/5359384/95414f325f1b/418_2016_1532_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e4f/5359384/7e3f037b8010/418_2016_1532_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e4f/5359384/95414f325f1b/418_2016_1532_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e4f/5359384/7e3f037b8010/418_2016_1532_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e4f/5359384/95414f325f1b/418_2016_1532_Fig2_HTML.jpg

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ATP6AP1 deficiency causes an immunodeficiency with hepatopathy, cognitive impairment and abnormal protein glycosylation.ATP6AP1 缺陷导致免疫缺陷伴肝病变、认知障碍和蛋白质糖基化异常。
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Deubiquitylase Inhibition Reveals Liver X Receptor-independent Transcriptional Regulation of the E3 Ubiquitin Ligase IDOL and Lipoprotein Uptake.
去泛素化酶抑制揭示了E3泛素连接酶IDOL和脂蛋白摄取的不依赖肝X受体的转录调控。
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Dysregulation of Plasmalogen Homeostasis Impairs Cholesterol Biosynthesis.缩醛磷脂稳态失调会损害胆固醇生物合成。
J Biol Chem. 2015 Nov 27;290(48):28822-33. doi: 10.1074/jbc.M115.656983. Epub 2015 Oct 13.
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Hum Mol Genet. 2015 Oct 15;24(20):5845-54. doi: 10.1093/hmg/ddv305. Epub 2015 Jul 28.
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