SR-BI mediates neutral lipid sorting from LDL to lipid droplets and facilitates their formation
| العنوان: | SR-BI mediates neutral lipid sorting from LDL to lipid droplets and facilitates their formation |
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| المؤلفون: | Tatyana G. Vishnyakova, Steven K. Drake, Thomas L. Eggerman, Marcelo Amar, Alexander V. Bocharov, Denis Sviridov, Roger Kurlander, Eugenia Poliakov, Boris L. Vaisman, Alan T. Remaley, Amy P. Patterson, Irina N. Baranova, Zhigang Chen |
| المصدر: | PLoS ONE, Vol 15, Iss 10, p e0240659 (2020) PLoS ONE |
| بيانات النشر: | Public Library of Science (PLoS), 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, Apolipoprotein B, Cultured tumor cells, Biochemistry, chemistry.chemical_compound, Lipid droplet, Enzyme Inhibitors, Mice, Knockout, Multidisciplinary, biology, Genetically Modified Organisms, Hydrolysis, Chemical Reactions, Animal Models, Scavenger Receptors, Class B, Lipids, Lipoproteins, LDL, Chemistry, Experimental Organism Systems, Liver, Physical Sciences, Cholesteryl ester, Cell lines, Engineering and Technology, Medicine, lipids (amino acids, peptides, and proteins), Neutral Lipids, Cholesterol Esters, Cellular Structures and Organelles, Triazenes, Biological cultures, Genetic Engineering, Research Article, Biotechnology, Boron Compounds, Lipoproteins, Science, Bioengineering, Mouse Models, 03 medical and health sciences, Model Organisms, Coenzyme A Ligases, Animals, Humans, HeLa cells, Scavenger receptor, Triglycerides, 030109 nutrition & dietetics, Genetically Modified Animals, Endoplasmic reticulum, Biology and Life Sciences, Proteins, Lipid metabolism, Biological Transport, Cell Biology, Lipid Droplets, Cell cultures, Molecular biology, De novo synthesis, Research and analysis methods, Mice, Inbred C57BL, 030104 developmental biology, chemistry, Receptors, LDL, LDL receptor, biology.protein, Animal Studies, Lysosomes |
| الوصف: | SR-BI binds various lipoproteins, including HDL, LDL as well as VLDL, and mediates selective cholesteryl ester (CE) uptake. HDL derived CE accumulates in cellular lipid droplets (LDs), which also store triacylglycerol (TAG). We hypothesized that SR-BI could significantly facilitate LD formation, in part, by directly transporting LDL derived neutral lipids (NL) such as CE and TAG into LDs without lipolysis and de novo lipid synthesis. SR-BI overexpression greatly increased LDL uptake and LD formation in stably transfected HeLa cells (SR-BI-HeLa). LDs isolated from SR-BI-HeLa contained 4- and 7-times more CE and TAG, respectively, than mock-transfected HeLa (Mock-HeLa). In contrast, LDL receptor overexpression in HeLa (LDLr-HeLa) greatly increased LDL uptake, degradation with moderate 1.5- and 2-fold increases of CE and TAG, respectively. Utilizing CE and TAG analogs, BODIPY-TAG (BP-TAG) and BODIPY-CE (BP-CE), for tracking LDL NL, we found that after initial binding of LDL to SR-BI-HeLa, apoB remained at the cell surface, while BP-CE and BP-TAG were sorted and simultaneously transported together to LDs. Both lipids demonstrated limited internalization to lysosomes or endoplasmic reticulum in SR-BI-HeLa. In LDLr-HeLa, NLs demonstrated clear lysosomal sequestration without their sorting to LDs. An inhibition of TAG and CE de novo synthesis by 90-95% only reduced TAG and CE LD content by 45-50%, and had little effect on BP-CE and BP-TAG transport to LDs in SR-BI HeLa. Furthermore, intravenous infusion of 1-2 mg of LDL increased liver LDs in normal (WT) but not in SR-BI KO mice. Mice transgenic for human SR-BI demonstrated higher liver LD accumulation than WT mice. Finally, Electro Spray Infusion Mass Spectrometry (ESI-MS) using deuterated d-CE found that LDs accumulated up to 40% of unmodified d-CE LDL. We conclude that SR-BI mediates LDL-induced LD formation in vitro and in vivo. In addition to cytosolic NL hydrolysis and de novo lipid synthesis, this process includes selective sorting and transport of LDL NL to LDs with limited lysosomal NL sequestration and the transport of LDL CE, and TAG directly to LDs independently of de novo synthesis. |
| اللغة: | English |
| تدمد: | 1932-6203 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::74a47cdd42c74ad55384c5029123e159 https://doaj.org/article/512639eae07b4c37b362ef2d1e422e9d |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....74a47cdd42c74ad55384c5029123e159 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19326203 |
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