)| PMID |
11223912 ( ) |
|---|---|
| Title | N-methyl-D-aspartate receptor-mediated mitochondrial Ca(2+) overload in acute excitotoxic motor neuron death: a mechanism distinct from chronic neurotoxicity after Ca(2+) influx. |
| Abstract | Mitochondrial uptake of Ca(2+) has recently been found to play an important role in glutamate-induced neurotoxicity (GNT) as well as in the activation of Ca(2+)-dependent molecules, such as calmodulin and neuronal nitric oxide synthase (nNOS), in the cytoplasm. Prolonged exposure to glutamate injures motor neurons predominantly through the activation of Ca(2+)/calmodulin-nNOS, as previously reported, and is, in part, associated with the pathogenesis of amyotrophic lateral sclerosis (ALS). In the present study, we investigated how mitochondrial uptake of Ca(2+) is involved in GNT in spinal motor neurons. Acute excitotoxicity induced by exposure to 0.5 mM glutamate for 5 min was found in both motor and nonmotor neurons in cultured spinal cords from rat embryos and was dependent on extracellular Ca(2+) and on N-methyl-D-aspartate (NMDA) receptor activation. Mitochondrial uncouplers markedly blocked acute excitotoxicity, and membrane-permeable superoxide dismutase mimics attenuated acute excitotoxicity induced by glutamate and NMDA but not by alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) or kainate. Fluorimetric analysis showed that mitochondrial Ca(2+) was elevated promptly with subsequent accumulation of reactive oxygen species (ROS) in the mitochondria. An NMDA receptor antagonist and a mitochondrial uncoupler eliminated the increase in fluorescence of mitochondrial Ca(2+) and ROS indicators. These data indicate that acute excitotoxicity in spinal neurons is mediated by mitochondrial Ca(2+) overload and ROS generation through the activation of NMDA receptors. This mechanism is different from that of chronic GNT. Sakyoku, Kyoto, Japan. |
NOTE: Color highlight is limited to the abstract and SciMiner text-mining mode. If you see much more identified targets below from "Targets by SciMiner Summary" and "Targets by SciMiner Full list", they may have been identified from the full text.
Targets by SciMiner Summary
| HUGO ID | Symbol | Target Name | #Occur | ActualStr |
|---|---|---|---|---|
| 7873 | NOS2A | nitric oxide synthase 2A (inducible, hepatocytes) | 2 | nitric oxide synthase | |
| 7872 | NOS1 | nitric oxide synthase 1 (neuronal) | 2 | nNOS | neuronal nitric oxide synthase | |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | 1 | superoxide dismutase | |
Targets by SciMiner Full list
| HUGO ID | Symbol | Name | ActualStr | Score | FlankingText |
|---|---|---|---|---|---|
| 7872 | NOS1 | nitric oxide synthase 1 (neuronal) | nNOS | 2.2 | molecules such as calmodulin and neuronal nitric oxide synthase (nNOS), nNOS in the cytoplasm |
| 7872 | NOS1 | nitric oxide synthase 1 (neuronal) | neuronal nitric oxide synthase | 1.0 | mitochondrial uptake of ca 2+ has recently been found to play an important role in glutamate induced neurotoxicity gnt as well as in the activation of ca 2+ dependent molecules such as calmodulin and neuronal nitric oxide synthase nnos in the cytoplasm. |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | superoxide dismutase | 1.0 | mitochondrial uncouplers markedly blocked acute excitotoxicity and membrane permeable superoxide dismutase mimics attenuated acute excitotoxicity induced by glutamate and nmda but not by alpha amino 3 hydroxy 5 methylisoxazole 4 propionate ampa or kainate. |
| 7873 | NOS2A | nitric oxide synthase 2A (inducible, hepatocytes) | nitric oxide synthase | 1.0 | phenylhydrazone|kainic acid|2 4 dinitrophenol|glutamic acid|calmidazolium|cyclosporine|n methylaspartate|calcium|dizocilpine maleate|alpha amino 3 hydroxy 5 methyl 4 isoxazolepropionic acid|dibucaine|nitric oxide synthase|nitric oxide synthase type i|nos1 protein rat|superoxide dismutase|calcium calmodulin dependent protein kinase type 2|calcium calmodulin dependent protein kinases| |
| 7873 | NOS2A | nitric oxide synthase 2A (inducible, hepatocytes) | nitric oxide synthase | 1.0 | |nitric oxide synthase type i|nos1 protein rat|superoxide dismutase|calcium calmodulin dependent protein kinase type 2|calcium calmodulin dependent protein kinases| |