Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.16.3.1 (ceruloplasmin)
 5,074 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Astrocytes play a key role in regulating aspects of inflammation and in the homeostatic maintenance of the central nervous system (CNS). However, the role of astrocytes in viral encephalitis mediated inflammation is not well documented. As Japanese encephalitis virus (JEV) infection is localized to neurons and considering the importance of astrocytes in supporting neuronal survival and function, we have exploited an experimental model of Japanese encephalitis (JE) to better understand the role of astrocytes in JE. Suckling mice pups were inoculated with the virus and 2 and 4 days later we analyzed a panel of molecules characteristic of reactive astrogliosis. We show that JEV infection increases the expression of astrocyte-specific glial fibrillary acidic protein (GFAP), the glutamate aspartate transporter (GLAST), glutamate transporter-1 (GLT-1) and ceruloplasmin (CP). The transcript levels of growth factors produced predominantly by activated astrocytes such as nerve growth factor (NGF) and ciliary neurotrophin factor (CNTF) were elevated following JEV infection. The transcript level of brain-derived neurotrophic factor (BDNF) was also elevated following JEV infection. Both NGF and CNTF were capable of preventing ROS mediated neuronal death following in vitro JEV infection to a certain extent. Taken altogether, these data indicate that increased astrogliosis following JEV infection is accompanied by the enhanced ability of astrocytes to detoxify glutamate, inactivate free radical and produce neurotrophic factors that are involved in neuronal protection. However, this elevated physiological state of astrocyte is insufficient in conferring neuroprotection, as infected animals eventually succumb to infection. The response of astrocytes to JE can be amplified to modulate the adaptive response of brain to induce neuroprotection.
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PMID:Neuroprotection conferred by astrocytes is insufficient to protect animals from succumbing to Japanese encephalitis. 1735 66

Hypoxic preconditioning reprogrammes the brain's response to subsequent H/I (hypoxia-ischaemia) injury by enhancing neuroprotective mechanisms. Given that astrocytes normally support neuronal survival and function, the purpose of the present study was to test the hypothesis that a hypoxic preconditioning stimulus would activate an adaptive astrocytic response. We analysed several functional parameters 24 h after exposing rat pups to 3 h of systemic hypoxia (8% O2). Hypoxia increased neocortical astrocyte maturation as evidenced by the loss of GFAP (glial fibrillary acidic protein)-positive cells with radial morphologies and the acquisition of multipolar GFAP-positive cells. Interestingly, many of these astrocytes had nuclear S100B. Accompanying their differentiation, there was increased expression of GFAP, GS (glutamine synthetase), EAAT-1 (excitatory amino acid transporter-1; also known as GLAST), MCT-1 (monocarboxylate transporter-1) and ceruloplasmin. A subsequent H/I insult did not result in any further astrocyte activation. Some responses were cell autonomous, as levels of GS and MCT-1 increased subsequent to hypoxia in cultured forebrain astrocytes. In contrast, the expression of GFAP, GLAST and ceruloplasmin remained unaltered. Additional experiments utilized astrocytes exposed to exogenous dbcAMP (dibutyryl-cAMP), which mimicked several aspects of the preconditioning response, to determine whether activated astrocytes could protect neurons from subsequent excitotoxic injury. dbcAMP treatment increased GS and glutamate transporter expression and function, and as hypothesized, protected neurons from glutamate excitotoxicity. Taken altogether, these results indicate that a preconditioning stimulus causes the precocious differentiation of astrocytes and increases the acquisition of multiple astrocytic functions that will contribute to the neuroprotection conferred by a sublethal preconditioning stress.
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PMID:Pre-conditioning induces the precocious differentiation of neonatal astrocytes to enhance their neuroprotective properties. 2172 95