Structure-based Design Targeted at LOX-1, a Receptor for Oxidized Low-Density Lipoprotein

التفاصيل البيبلوغرافية
العنوان: Structure-based Design Targeted at LOX-1, a Receptor for Oxidized Low-Density Lipoprotein
المؤلفون: Yao Dai, Magomed Khaidakov, Shraddha Thakkar, Kuppan Gokulan, Kottayil I. Varughese, Xianwei Wang, Jawahar L. Mehta
المصدر: Scientific Reports
بيانات النشر: Springer Science and Business Media LLC, 2015.
سنة النشر: 2015
مصطلحات موضوعية: Models, Molecular, p38 mitogen-activated protein kinases, Molecular Conformation, Gene Expression, Vascular Cell Adhesion Molecule-1, Plasma protein binding, Biology, Ligands, Article, Small Molecule Libraries, Structure-Activity Relationship, chemistry.chemical_compound, Drug Discovery, Gene expression, Cell Adhesion, Human Umbilical Vein Endothelial Cells, Humans, Computer Simulation, Protein Interaction Domains and Motifs, Scavenger receptor, Cell adhesion, Receptor, Regulation of gene expression, Multidisciplinary, Protein Stability, Scavenger Receptors, Class E, Cell biology, Lipoproteins, LDL, Gene Expression Regulation, chemistry, Drug Design, Low-density lipoprotein, lipids (amino acids, peptides, and proteins), Mitogen-Activated Protein Kinases, Protein Binding
الوصف: Atherosclerosis related cardiovascular diseases continue to be the primary cause of mortality in developed countries. The elevated level of low density lipoprotein (LDL) is generally considered to be the driver of atherosclerosis, but recent years have seen a shift in this perception in that the vascular plaque buildup is mainly caused by oxidized LDL (ox-LDL) rather than native-LDL. The scavenger receptor LOX-1 found in endothelial cells binds and internalizes ox-LDL which leads to the initiation of plaque formation in arteries. Using virtual screening techniques, we identified a few potential small molecule inhibitors of LOX-1 and tested their inhibitory potential using differential scanning fluorimetry and various cellular assays. Two of these molecules significantly reduced the uptake of ox-LDL by human endothelial cells, LOX-1 transcription and the activation of ERK1/2 and p38 MAPKs in human endothelial cells. In addition, these molecules suppressed ox-LDL-induced VCAM-1 expression and monocyte adhesion onto human endothelial cells demonstrating their therapeutic potential.
تدمد: 2045-2322
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c2d157302ffce0fd1d31d91465f6a5abTest
https://doi.org/10.1038/srep16740Test
حقوق: OPEN
رقم الانضمام: edsair.doi.dedup.....c2d157302ffce0fd1d31d91465f6a5ab
قاعدة البيانات: OpenAIRE