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DOI | 10.1038/s41467-019-11525-x |
Oxidized phospholipids regulate amino acid metabolism through MTHFD2 to facilitate nucleotide release in endothelial cells | |
Hitzel, Juliane1,2; Lee, Eunjee3,4; Zhang, Yi3,5; Bibli, Sofia Iris2,6; Li, Xiaogang7; Zukunft, Sven2,6; Pflueger, Beatrice1,2; Hu, Jiong2,6; Schuermann, Christoph1,2; Vasconez, Andrea Estefania1,2; Oo, James A.1,2; Kratzer, Adelheid8,9; Kumar, Sandeep10,11; Rezende, Flavia1,2; Josipovic, Ivana1,2; Thomas, Dominique12; Giral, Hector8,9; Schreiber, Yannick13; Geisslinger, Gerd12,13; Fork, Christian1,2; Yang, Xia14; Sigala, Fragiska15; Romanoski, Casey E.16; Kroll, Jens7; Jo, Hanjoong10,11; Landmesser, Ulf8,9,17; Lusis, Aldons J.18,19; Namgaladze, Dmitry20; Fleming, Ingrid2,6; Leisegang, Matthias S.1,2; Zhu, Jun3,4; Brandes, Ralf P.1,2 | |
2019-08-08 | |
发表期刊 | NATURE COMMUNICATIONS |
ISSN | 2041-1723 |
出版年 | 2018 |
卷号 | 9 |
文章类型 | Article |
语种 | 英语 |
国家 | Germany; USA; Peoples R China; Greece |
英文摘要 | Oxidized phospholipids (oxPAPC) induce endothelial dysfunction and atherosclerosis. Here we show that oxPAPC induce a gene network regulating serine-glycine metabolism with the mitochondrial methylenetetrahydrofolate dehydrogenase/cyclohydrolase (MTHFD2) as a causal regulator using integrative network modeling and Bayesian network analysis in human aortic endothelial cells. The cluster is activated in human plaque material and by atherogenic lipoproteins isolated from plasma of patients with coronary artery disease (CAD). Single nucleotide polymorphisms (SNPs) within the MTHFD2-controlled cluster associate with CAD. The MTHFD2-controlled cluster redirects metabolism to glycine synthesis to replenish purine nucleotides. Since endothelial cells secrete purines in response to oxPAPC, the MTHFD2-controlled response maintains endothelial ATP. Accordingly, MTHFD2-dependent glycine synthesis is a prerequisite for angiogenesis. Thus, we propose that endothelial cells undergo MTHFD2-mediated reprogramming toward serine-glycine and mitochondrial one-carbon metabolism to compensate for the loss of ATP in response to oxPAPC during atherosclerosis. |
领域 | 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000434927000001 |
WOS关键词 | UNFOLDED PROTEIN RESPONSE ; CORONARY-ARTERY-DISEASE ; ATP RELEASE ; GENE-EXPRESSION ; SEGREGATING POPULATIONS ; VASCULAR MORPHOGENESIS ; CANCER-CELLS ; ER STRESS ; ATHEROSCLEROSIS ; NETWORKS |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
URL | 查看原文 |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/204492 |
专题 | 资源环境科学 |
作者单位 | 1.Goethe Univ, Inst Cardiovasc Physiol, D-60590 Frankfurt, Germany; 2.German Ctr Cardiovasc Res DZHK, Partner Site Rhine Main, D-60590 Frankfurt, Germany; 3.Mt Sinai Icahn Sch Med, Icahn Inst Genom & Multiscale Biol, New York, NY 10029 USA; 4.Sema4 Genom, Stamford, CT 06902 USA; 5.Hebei Univ Sci & Technol, Dept Math, Shijiazhuang 050018, Hebei, Peoples R China; 6.Goethe Univ, Inst Vasc Signalling, Ctr Mol Med, D-60590 Frankfurt, Germany; 7.Heidelberg Univ, Med Fac Mannheim, European Ctr Angiosci ECAS, Dept Vasc Biol & Tumor Angiogenesis, D-68167 Mannheim, Germany; 8.Charite Univ Med Berlin, Dept Cardiol, Campus Benjamin Franklin, D-12203 Berlin, Germany; 9.German Ctr Cardiovasc Res DZHK, Partner Site Berlin, D-13316 Berlin, Germany; 10.Georgia Inst Technol, Wallace H Coulter Dept Biomed Engn, Atlanta, GA 30332 USA; 11.Emory Univ, Atlanta, GA 30332 USA; 12.Goethe Univ, Fac Med, Inst Clin Pharmacol, Pharmazentrum Frankfurt ZAFES, D-60590 Frankfurt, Germany; 13.Fraunhofer Inst Mol Biol & Appl Ecology, Project Grp Translat Med & Pharmacol IME TMP, D-60596 Frankfurt, Germany; 14.Univ Calif Los Angeles, Dept Integrat Biol & Physiol, Los Angeles, CA 90095 USA; 15.Univ Athens, Med Sch, Hippocrat Hosp, Dept Propaedeut Surg 1, Athens 11364, Greece; 16.Univ Arizona, Dept Cellular & Mol Med, Tucson, AZ 85724 USA; 17.BIH, D-10178 Berlin, Germany; 18.Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90095 USA; 19.Univ Calif Los Angeles, Dept Microbiol & Human Genet, Los Angeles, CA 90095 USA; 20.Goethe Univ, Inst Biochem 1, D-60590 Frankfurt, Germany |
推荐引用方式 GB/T 7714 | Hitzel, Juliane,Lee, Eunjee,Zhang, Yi,et al. Oxidized phospholipids regulate amino acid metabolism through MTHFD2 to facilitate nucleotide release in endothelial cells[J]. NATURE COMMUNICATIONS,2019,9. |
APA | Hitzel, Juliane.,Lee, Eunjee.,Zhang, Yi.,Bibli, Sofia Iris.,Li, Xiaogang.,...&Brandes, Ralf P..(2019).Oxidized phospholipids regulate amino acid metabolism through MTHFD2 to facilitate nucleotide release in endothelial cells.NATURE COMMUNICATIONS,9. |
MLA | Hitzel, Juliane,et al."Oxidized phospholipids regulate amino acid metabolism through MTHFD2 to facilitate nucleotide release in endothelial cells".NATURE COMMUNICATIONS 9(2019). |
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