Modulation of cell proteome by 25-hydroxycholesterol and 27-hydroxycholesterol: A link between cholesterol metabolism and antiviral defense
| العنوان: | Modulation of cell proteome by 25-hydroxycholesterol and 27-hydroxycholesterol: A link between cholesterol metabolism and antiviral defense |
|---|---|
| المؤلفون: | Valeria Cagno, Andrea Civra, Mara Colzani, David Lembo, Valerio Leoni, Giancarlo Aldini, Giuseppe Poli, Rachele Francese |
| المساهمون: | Civra, A, Colzani, M, Cagno, V, Francese, R, Leoni, V, Aldini, G, Lembo, D, Poli, G |
| المصدر: | Free Radical Biology & Medicine |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, Proteome, Endosome, Cell, Antiviral Agents, Biochemistry, Article, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Oxysterol, Viral entry, Physiology (medical), polycyclic compounds, medicine, Humans, Antiviral activity, Receptor, 25-Hydroxycholesterol, 27-Hydroxycholesterol, Oxysterols, SILAC proteomics, Sterol metabolism, Chemistry, Cell adhesion molecule, Hydroxycholesterols, Cell biology, 030104 developmental biology, medicine.anatomical_structure, Viral replication, lipids (amino acids, peptides, and proteins), 030217 neurology & neurosurgery, SILAC proteomic |
| الوصف: | Physiological cholesterol metabolism implies the generation of a series of oxidized derivatives, whose oxysterols are by far the most investigated ones for their potential multifaceted involvement in human pathophysiology. In this regard, noteworthy is the broad antiviral activity displayed by defined side chain oxysterols, in particular 25-hydroxycholesterol (25HC) and 27-hydroxycholesterol (27HC). Although their antiviral mechanism(s) may vary depending on virus/host interaction, these oxysterols share the common feature to hamper viral replication by interacting with cellular proteins. Here reported is the first analysis of the modulation of a cell proteome by these two oxysterols, that, besides yielding additional clues about their potential involvement in the regulation of sterol metabolism, provides novelinsights about the mechanism underlying the inhibition of virus entry and trafficking within infected cells. We show here that both 25HC and 27HC can down-regulate the junction adhesion molecule-A (JAM-A) and the cation independent isoform of mannose-6-phosphate receptor (MPRci), two crucial molecules for the replication of all those viruses that exploit adhesion molecules and the endosomal pathway to enter and diffuse within target cells. Graphical abstract Image 1 Highlights • 25HC and 27HC, two physiological products of enzymatic cholesterol oxidation, modulate the proteome of HeLa cells, standard model system. • Cell proteome analysis was afforded by coupling mass spectrometry to stable isotope labelling by amino acids in cell culture (SILAC) technology. • The large majority of proteins significantly modulated by both 25HC and 27HC is related to sterol synthesis and metabolism. • Down-regulation of JAM-A and MPRci likely contributes to the broad antiviral activity of 25HC and 27HC. |
| وصف الملف: | STAMPA |
| اللغة: | English |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d6f4ab4fc1055a6009ccfff6c7932657 http://hdl.handle.net/2318/1768419 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....d6f4ab4fc1055a6009ccfff6c7932657 |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |