The HIV-1 Nef Protein Inhibits Extracellular Signal-Regulated Kinase-Dependent DNA Synthesis in a Human Astrocytic Cell Line
| العنوان: | The HIV-1 Nef Protein Inhibits Extracellular Signal-Regulated Kinase-Dependent DNA Synthesis in a Human Astrocytic Cell Line |
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| المؤلفون: | Alexandra Teixeira, Pierre-Olivier Couraud, A. Donny Strosberg, Ignacio A. Romero, Sylvie Cazaubon |
| المصدر: | Journal of Neurochemistry. 70:778-785 |
| بيانات النشر: | Wiley, 2002. |
| سنة النشر: | 2002 |
| مصطلحات موضوعية: | DNA Replication, MAPK/ERK pathway, Receptors, CCR4, viruses, Astrocytoma, Biology, Transfection, Biochemistry, Gene Products, nef, Cell Line, Focal adhesion, Cellular and Molecular Neuroscience, chemistry.chemical_compound, Chemokine receptor, Humans, nef Gene Products, Human Immunodeficiency Virus, Protein kinase A, Protein kinase C, Mitogen-Activated Protein Kinase 1, Endothelin-1, DNA synthesis, Kinase, virus diseases, Tyrosine phosphorylation, Protein-Tyrosine Kinases, Recombinant Proteins, Cell biology, Enzyme Activation, chemistry, Astrocytes, Focal Adhesion Kinase 1, Focal Adhesion Protein-Tyrosine Kinases, Calcium-Calmodulin-Dependent Protein Kinases, HIV-1, Receptors, Chemokine, Cell Adhesion Molecules |
| الوصف: | The role of nonproductive infection of astrocytes by human immunodeficiency virus type 1 (HIV-1), characterized by the overexpression of nef, in brain disease progression is largely unknown. We investigated the consequences of stable expression of nef from the HIV-1 strain LAI in the human astrocytic cell line U373. DNA synthesis induced by endothelin-1 (ET-1) was largely decreased by nef. Stable expression of nef did not affect the ET-1-induced tyrosine phosphorylation of focal adhesion kinase, an adhesion-dependent pathway known to participate in DNA synthesis in astrocytes. Conversely, the activation of extracellular signal-regulated kinase (ERK) by ET-1 was largely inhibited in cells stably or transiently expressing nef. A similar inhibitory action of nef on ERK activation was observed after direct stimulation of G proteins. Furthermore, the inhibitory action of nef did not require protein kinase C (PKC) and affected mainly the PKC-independent pathway of ERK activation. Following chemokine receptor CXCR4-mediated infection of U373 cells stably expressing CXCR4 with the T-tropic HIV-1 strain m7-NDK, ET-1-induced activation of ERK was also inhibited. Altogether, these results indicate that intracellular signaling pathways associated with the growth factor activity of ET-1 are impaired in nef-expressing and HIV-1-infected astrocytes, suggesting that infection of astrocytes may play a significant role in the neuropathogenesis of HIV-1 encephalopathy. |
| تدمد: | 1471-4159 0022-3042 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a2ba9c665fa949a5c89fbcfebc7aa69dTest https://doi.org/10.1046/j.1471-4159.1998.70020778.xTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....a2ba9c665fa949a5c89fbcfebc7aa69d |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14714159 00223042 |
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