Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.22.60 (caspase-7)
 920 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The neurotransmitter glutamate mediates excitatory synaptic transmission in the brain and spinal cord. In pathological conditions massive glutamate release reaches near millimolar concentrations in the extracellular space and contributes to neuron degeneration and death. In the present study, we demonstrate a neuroprotective role for human umbilical cord blood stem cells (hUCB) against glutamate-induced apoptosis in cultured rat cortical neurons. Microarray analysis shows the upregulation of stress pathway genes after glutamate toxicity of neurons, while in cocultures with hUCB, survival pathway genes were upregulated. Real time-PCR analysis shows the expression of genes for NMDA receptors after glutamate toxicity in neurons. The neuroprotection of hUCB against glutamate toxicity is similar to the application of the glutamate receptor antagonist MK-801. Cocultures of hUCB protected neurons against glutamate-induced apoptosis as revealed by APO-BrdU TUNEL and FACS analyses. Immunoblot analysis shows that apoptosis is mediated by the cleavage of caspase-3 and caspase-7 in glutamate treated neurons. Cocultures with hUCB indicate the upregulation of Akt signaling pathway to protect neurons. Blocking of the Akt pathway by a dominant-negative Akt and using Akt-inhibitor IV, we confirm that the mechanism underlying hUCB neuroprotection involves activation of Akt signaling pathway. These results suggest the neuroprotective potential of hUCB against glutamate-induced apoptosis of cultured cortical neurons.
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PMID:Neuroprotection by cord blood stem cells against glutamate-induced apoptosis is mediated by Akt pathway. 1893 Jan 39

In the present study, we investigated whether cultured astrocytes derived from adult neural precursor cells (NPCs) obtained from the subventricular zone (SVZ) of wobbler mice display metabolic traits of the wobbler astrocytes in situ and in primary culture. We also utilized NPC-derived astrocytes as a tool to investigate the involvement of astrocytes in the molecular mechanism of MND focusing on the possible alteration of glutamate reuptake since excitotoxicity glutamate-mediated may be a contributory pathway. NPC-derived wobbler astrocytes are characterized by high immunoreactivity for GFAP, significant decrease of glutamate uptake and reduced immunoreactivity for glutamate transporters GLT1 and GLAST. Spinal cord motor neurons obtained from healthy mouse embryos, when co-cultured with wobbler NPC-derived astrocytes, show reduced viability and morphologic alterations. These suffering motor neurons are caspase-7 positive, and treatment with anti-apoptotic drug V5 increases cell survival. Physical contact with wobbler astrocytes is not essential because purified motor neurons display reduced survival also when treated with the medium conditioned by wobbler NPC-derived astrocytes. Toxic levels of glutamate were revealed by HPLC assay in the extracellular medium of wobbler NPC-derived astrocytes, whereas the level of intracellular glutamate is reduced if compared with controls. Moreover, glutamate receptor antagonists are able to enhance motor neuron survival. Therefore, our results demonstrate that astrocytes derived from wobbler neural precursor cells display impaired glutamate homeostasis that may play a crucial role in motor neuron degeneration. Finally, the cultured astrocytes derived from NPCs of adult mice may offer a useful alternative in vitro model to study the molecular mechanisms involved in neurodegeneration.
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PMID:Neural precursor-derived astrocytes of wobbler mice induce apoptotic death of motor neurons through reduced glutamate uptake. 2055 60