文章基本信息

标题：SAR1B GTPase is necessary to protect intestinal cells from disorders of lipid homeostasis, oxidative stress, and inflammation
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作者：Alain Sané ; Lena Ahmarani ; Edgard Delvin 等
期刊名称：JLR Papers In Press
印刷版ISSN：0022-2275
电子版ISSN：1539-7262
出版年度：2019
卷号：60
期号：10
页码：1755-1764
DOI：10.1194/jlr.RA119000119
出版社：American Society for Biochemistry and Molecular Biology
摘要：Genetic defects in SAR1B GTPase inhibit chylomicron (CM) trafficking to the Golgi and result in a huge intraenterocyte lipid accumulation with a failure to release CMs and liposoluble vitamins into the blood circulation. The central aim of this study is to test the hypothesis that SAR1B deletion ( SAR1B^−/− ) disturbs enterocyte lipid homeostasis (e.g., FA β-oxidation and lipogenesis) while promoting oxidative stress and inflammation. Another issue is to compare the impact of SAR1B^−/− to that of its paralogue SAR1A^−/− and combined SAR1A^−/− / B^−/− . To address these critical issues, we have generated Caco-2/15 cells with a knockout of SAR1A , SAR1B , or SAR1A/B genes. SAR1B^−/− results in lipid homeostasis disruption, reflected by enhanced mitochondrial FA β-oxidation and diminished lipogenesis in intestinal absorptive cells via the implication of PPARα and PGC1α transcription factors. Additionally, SAR1B ^−/− cells, which mimicked enterocytes of CM retention disease, spontaneously disclosed inflammatory and oxidative characteristics via the implication of NF-κB and NRF2. In most conditions, SAR1A^−/− cells showed a similar trend, albeit less dramatic, but synergetic effects were observed with the combined defects of the two SAR1 paralogues. In conclusion, SAR1B and its paralogue are needed not only for CM trafficking but also for lipid homeostasis, prooxidant/antioxidant balance, and protection against inflammatory processes.
关键词：gene silencing ; SAR1 paralogues ; triglyceride-rich lipoproteins ; metabolism ; mitochondria ; intestine ; transcription factors