Modulation of α-Enolase Post-Translational Modifications by Dengue Virus: Increased Secretion of the Basic Isoforms in Infected Hepatic Cells
| العنوان: | Modulation of α-Enolase Post-Translational Modifications by Dengue Virus: Increased Secretion of the Basic Isoforms in Infected Hepatic Cells |
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| المؤلفون: | Cynthia Chester Cardoso, Russolina B. Zingali, Luiza M. Higa, André G. De Lorenzi, Andrea T. Da Poian, Bruno M. Curi, Renato S. Aguiar, Silvia L. F. Sena |
| المصدر: | PLoS ONE PLoS ONE, Vol 9, Iss 8, p e88314 (2014) |
| بيانات النشر: | Public Library of Science, 2014. |
| سنة النشر: | 2014 |
| مصطلحات موضوعية: | Viral Diseases, Pathogenesis, Dengue virus, medicine.disease_cause, Pathology and Laboratory Medicine, Virus Replication, Biochemistry, Dengue fever, Dengue Fever, 0302 clinical medicine, Molecular Cell Biology, Medicine and Health Sciences, 0303 health sciences, Multidisciplinary, medicine.diagnostic_test, Hep G2 Cells, 3. Good health, Blot, Isoenzymes, Infectious Diseases, 030220 oncology & carcinogenesis, Host-Pathogen Interactions, Medicine, Molecular Pathology, Research Article, Neglected Tropical Diseases, Gene isoform, Science, Biology, Microbiology, 03 medical and health sciences, Western blot, Virology, medicine, Humans, Antibody-dependent enhancement, Secretion, 030304 developmental biology, Biology and Life Sciences, Cell Biology, Dengue Virus, medicine.disease, Tropical Diseases, Molecular biology, Phosphopyruvate Hydratase, Hepatic stellate cell, Hepatocytes, Protein Processing, Post-Translational |
| الوصف: | Hepatic cells are major sites of dengue virus (DENV) replication and liver injury constitutes a characteristic of severe forms of dengue. The role of hepatic cells in dengue pathogenesis is not well established, but since hepatocytes are the major source of plasma proteins, changes in protein secretion by these cells during infection might contribute to disease progression. Previously, we showed that DENV infection alters the secretion pattern of hepatic HepG2 cells, with α-enolase appearing as one of the major proteins secreted in higher levels by infected cells. ELISA analysis demonstrated that DENV infection modulates α-enolase secretion in HepG2 cells in a dose-dependent manner, but has no effect on its gene expression and on the intracellular content of the protein as assessed by PCR and western blot analyses, respectively. Two-dimensional western blots showed that both intracellular and secreted forms of α-enolase appear as five spots, revealing α-enolase isoforms with similar molecular weights but distinct isoeletric points. Remarkably, quantification of each spot content revealed that DENV infection shifts the isoform distribution pattern of secreted α-enolase towards the basic isoforms, whereas the intracellular protein remains unaltered, suggesting that post-translational modifications might be involved in α-enolase secretion by infected cells. These findings provide new insights into the mechanisms underlying α-enolase secretion by hepatic cells and its relationship with the role of liver in dengue pathogenesis. In addition, preliminary results obtained with plasma samples from DENV-infected patients suggest an association between plasma levels of α-enolase and disease severity. Since α-enolase binds plasminogen and modulates its activation, it is plausible to speculate the association of the increase in α-enolase secretion by infected hepatic cells with the haemostatic dysfunction observed in dengue patients including the promotion of fibrinolysis and vascular permeability alterations. |
| اللغة: | English |
| تدمد: | 1932-6203 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d81cc0a4ae784492db334132a01f65ab http://europepmc.org/articles/PMC4149363 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....d81cc0a4ae784492db334132a01f65ab |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19326203 |
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