| Autor: |
Zhao J; Laboratory of Neurotoxicology at the Center for Neurovirology and Neurodegenerative Disorders Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, Nebraska 68198-5215, USA., Lopez AL, Erichsen D, Herek S, Cotter RL, Curthoys NP, Zheng J |
| Jazyk: |
angličtina |
| Zdroj: |
Journal of neurochemistry [J Neurochem] 2004 Jan; Vol. 88 (1), pp. 169-80. |
| DOI: |
10.1046/j.1471-4159.2003.02146.x |
| Abstrakt: |
Dysfunction in mononuclear phagocyte (MP, macrophages and microglia) immunity is thought to play a significant role in the pathogenesis of HIV-1 associated dementia (HAD). In particular, elevated extracellular concentrations of the excitatory neurotransmitter glutamate, produced by MP as a consequence of viral infection and immune activation, can induce neuronal injury. To determine the mechanism by which MP-mediated neuronal injury occurs, the concentration and rates of production of extracellular glutamate were measured in human monocyte-derived macrophage (MDM) supernatants by reverse phase high-performance liquid chromatography (RP-HPLC). Measurements were taken of supernatants from MDM infected with multiple HIV-1 strains including ADA and DJV (macrophage tropic, M-tropic), and 89.6 (dual tropic). High levels of glutamate were produced by MDM infected with M-tropic viruses. AZT, an inhibitor of HIV-1 replication, inhibited glutamate generation, demonstrating a linkage between HIV-1 infection and enhanced glutamate production. In our culture system, glutamate production was dependent upon the presence of glutamine and was inhibited by 6-diazo-5-oxo-L-norleucine, a glutaminase inhibitor. Supernatants collected from HIV-1-infected MP generated more glutamate following glutamine addition than supernatants isolated from uninfected MP. These findings implicate the involvement of a glutamate-generating enzyme, such as phosphate-activated mitochondrial glutaminase (PMG) in MP-mediated glutamate production. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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