Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027819 (neuroblastoma)
 27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ischemic stroke causes a significant amount of cell damage resulting from an insufficient supply of glucose and oxygen to central nervous system tissue and finding more effective therapeutic neuroprotective agents has become a priority in the treatment of ischemic stroke. Hsp20, one of the small heat shock proteins, has been implicated in multiple physiological and pathophysiological processes and is a potential neuroprotective agents. To investigate whether Hsp20 exerts protective effects on in vitro ischemia-reperfusion injury, mouse neuroblastoma cells were subjected to oxygen-glucose deprivation/reoxygenation (OGDR) insult. The N2a cells transfected with Hsp20 and constitutively phosphorylated Hsp20 (S16D) had significantly less cell loss and less proportion of apoptotic cells compared to N2a cells transfected with pEGFP-N1 after oxygen-glucose deprivation (OGD) 4 h plus 12 and 24 h reperfusion, which showed no difference in N2a cells transfected with nonphosphorylatable Hsp20 (S16A). Meanwhile, transfected with Hsp20 and constitutively phosphorylated Hsp20 (S16D) also significantly attenuated mitochondrial fragmentation and modulated Bcl-2 and Bax expression level after OGD 4 h plus 12 reperfusion, which were not affected in N2a cells transfected with Hsp20 (S16A). In conclusion, our data demonstrated that increased Hsp20 and Hsp20 (S16D) expression in mouse N2A neuroblastoma cells protected against ischemia-reperfusion injury, the neuroprotective mechanism may be related to regulate Bcl-2 and Bax expression. However, blockade of Ser16-Hsp20 phosphorylation attenuated the neuroprotective effects of Hsp20. Therefore, Hsp20 and factors that contribute to regulation of phosphorylation on Ser16 of Hsp20 are potential new therapeutic targets for the treatment of cerebral ischemia-reperfusion injury.
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PMID:Blockade of Ser16-Hsp20 phosphorylation attenuates neuroprotection dependent upon Bcl-2 and Bax. 2371 35

Ischemic stroke is an acute vascular event that obstructs blood supply to the brain, producing irreversible damage that affects neurons but also glial and brain vessel cells. Immediately after the stroke, the ischemic tissue produces nitric oxide (NO) to recover blood perfusion but also produces superoxide anion. These compounds interact, producing peroxynitrite, which irreversibly nitrates protein tyrosines. The present study measured NO production in a human neuroblastoma (SH-SY5Y), a murine glial (BV2), a human endothelial cell line (HUVEC), and in primary cultures of human cerebral myocytes (HC-VSMCs) after experimental ischemia in vitro. Neuronal, endothelial, and inducible NO synthase (NOS) expression was also studied up to 24 h after ischemia, showing a different time course depending on the NOS type and the cells studied. Finally, we carried out cell viability experiments on SH-SY5Y cells with H2O2, a prooxidant agent, and with a NO donor to mimic ischemic conditions. We found that both compounds were highly toxic when they interacted, producing peroxynitrite. We obtained similar results when all cells were challenged with peroxynitrite. Our data suggest that peroxynitrite induces cell death and is a very harmful agent in brain ischemia.
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PMID:Nitro-oxidative stress after neuronal ischemia induces protein nitrotyrosination and cell death. 2398 1

Ischemic stroke is an acute vascular event that compromises neuronal viability, and identification of the pathophysiological mechanisms is critical for its correct management. Ischemia produces increased nitric oxide synthesis to recover blood flow but also induces a free radical burst. Nitric oxide and superoxide anion react to generate peroxynitrite that nitrates tyrosines. We found that fibrinogen nitrotyrosination was detected in plasma after the initiation of ischemic stroke in human patients. Electron microscopy and protein intrinsic fluorescence showed that in vitro nitrotyrosination of fibrinogen affected its structure. Thromboelastography showed that initially fibrinogen nitrotyrosination retarded clot formation but later made the clot more resistant to fibrinolysis. This result was independent of any effect on thrombin production. Immunofluorescence analysis of affected human brain areas also showed that both fibrinogen and nitrotyrosinated fibrinogen spread into the brain parenchyma after ischemic stroke. Therefore, we assayed the toxicity of fibrinogen and nitrotyrosinated fibrinogen in a human neuroblastoma cell line. For that purpose we measured the activity of caspase-3, a key enzyme in the apoptotic pathway, and cell survival. We found that nitrotyrosinated fibrinogen induced higher activation of caspase 3. Accordingly, cell survival assays showed a more neurotoxic effect of nitrotyrosinated fibrinogen at all concentrations tested. In summary, nitrotyrosinated fibrinogen would be of pathophysiological interest in ischemic stroke due to both its impact on hemostasis - it impairs thrombolysis, the main target in stroke treatments - and its neurotoxicity that would contribute to the death of the brain tissue surrounding the infarcted area.
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PMID:Fibrinogen nitrotyrosination after ischemic stroke impairs thrombolysis and promotes neuronal death. 2550 Jan 53

Ischemic stroke results in severe brain damage and remains one of the leading causes of death and disability worldwide. Effective neuroprotective therapies are needed to reduce brain damage resulting from ischemic stroke. Mitochondria are crucial for cellular energy production and homeostasis. Modulation of mitochondrial function mediates neuroprotection against ischemic brain damage. Dynamin-related protein 1 (Drp1) and parkin play a key role in regulating mitochondrial dynamics. They are potential therapeutic targets for neuroprotection in ischemic stroke. Protective effects of parkin-Drp1 pathway on mitochondria were assessed in a cellular ischemia-reperfusion injury model. Mouse neuroblastoma Neuro2a (N2a) cells were subjected to oxygen-glucose deprivation/reperfusion (OGDR) insult. OGDR induces mitochondrial fragmentation. The expression of Drp1 protein is increased after OGDR insult, while the parkin protein level is decreased. The altered protein level of Drp1 after OGDR injury is mediated by parkin through ubiquitin proteasome system (UPS). Drp1 depletion protects against OGDR induced mitochondrial damage and apoptosis. Meanwhile, parkin overexpression protects against OGDR induced apoptosis and mitochondrial dysfunction, which is attenuated by increased expression of Drp1. Our data demonstrate that parkin protects against OGDR insult through promoting degradation of Drp1. This neuroprotective potential of parkin-Drp1 pathway against OGDR insult will pave the way for developing novel neuroprotective agents for cerebral ischemia-reperfusion related disorders.
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PMID:Parkin Protects against Oxygen-Glucose Deprivation/Reperfusion Insult by Promoting Drp1 Degradation. 2759 85