IL‐1β and TNF‐α induce neurotoxicity through glutamate production: a potential role for neuronal glutaminase

• DOI: 10.1111/jnc.12263
• Publication Date: 2013-04-11T16:36:43Z
• Authors: Ling Ye; Yunlong Huang; Lixia Zhao; Yuju Li; Lijun Sun; You Zhou; Guanxiang Qian; Jialin C. Zheng
• Keywords: Neurotoxicity; Glutaminase; Neurotoxin

Glutaminase 1 is the main enzyme responsible for glutamate production in mammalian cells. The roles of macrophage and microglia glutaminases brain injury, infection, inflammation are well documented. However, little known about regulation neuronal glutaminase, despite neurons being a predominant cell type glutaminase expression. Using primary rat human cultures, we confirmed that interleukin-1β (IL-1β) tumor necrosis factor-α (TNF-α), two pro-inflammatory cytokines typically elevated neurodegenerative disease states, induced death apoptosis vitro. Furthermore, both intracellular extracellular levels were significantly following IL-1β and/or TNF-α treatment. Pre-treatment with N-Methyl-D-aspartate (NMDA) receptor antagonist MK-801 blocked cytokine-induced alleviated neurotoxicity, indicating induce neurotoxicity through glutamate. To determine potential source excess culture during inflammation, investigated found treatment or upregulated kidney-type (KGA), isoform, neurons. up-regulation was also demonstrated situ murine model HIV-1 encephalitis. In addition, increased KGA cytosol specifically fluid, away from its residence mitochondria. Together, these findings support as component modulation may provide therapeutic avenues diseases.