| Nerve growth factor pretreatment attenuates oxygen and glucose deprivation-induced c-Jun amino-terminal kinase 1 and stress-activated kinases p38alpha and p38beta activation and confers neuroprotection in the pheochromocytoma PC12 Model. | |
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MedLine Citation:
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PMID: 14997018 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Neurotrophins such as nerve growth factor (NGF) are considered putative neuroprotective compounds in the central nervous system. To investigate the cellular and molecular neuroprotective mechanisms of NGF under ischemia, we used a unique oxygen and glucose deprivation (OGD) device. In this system we used pheochromocytoma PC12 cells to elucidate NGF neuroprotective effect. PC12 cells were exposed to OGD, followed by addition of glucose and oxygen (OGD reperfusion). Neuronal cell death induced in this model was measured by the release of lactate dehydrogenase (LDH), activation of caspase-3 and mitogen-activated protein kinases (MAPKs), measured with specific anti-phospho-antibodies. Pretreatment of the cultures with 50 ng/mL NGF, 18 h prior to OGD insult, conferred 30% neuroprotection. However, treatment of the cultures with NGF concomitantly with the OGD insult did not result in neuroprotection. Time-course experiments showed marked activation of extracellular signal-regulated protein kinase, c-Jun N-terminal kinase (JNK), and p38 MAPK isoforms during the OGD phase but not during OGD reperfusion. Pretreatment of the cultures with 50 ng/mL NGF, 18 h prior to OGD insult, resulted in 50% attenuation of OGD-induced activation of JNK1, and 20% and 50% attenuation of OGD-induced activation of p38alpha and beta, respectively. These findings support the notion that NGF confers neuroprotection from OGD insult, a phenomenon coincidentally related to differential inhibition of MAPK stress kinase isoforms, and provide the PC12 model as an in vitro OGD system to investigate molecular mechanisms of neurotoxicity and neuroprotection. |
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Authors:
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Rinat Tabakman; Hao Jiang; Erik Schaefer; Robert A Levine; Philip Lazarovici |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Journal of molecular neuroscience : MN Volume: 22 ISSN: 0895-8696 ISO Abbreviation: J. Mol. Neurosci. Publication Date: 2004 |
Date Detail:
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Created Date: 2004-03-03 Completed Date: 2004-06-17 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 9002991 Medline TA: J Mol Neurosci Country: United States |
Other Details:
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Languages: eng Pagination: 237-50 Citation Subset: IM |
Affiliation:
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Department of Pharmacology and Experimental Therapeutics, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 91120, Israel. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Brain Ischemia / drug therapy*, enzymology* Caspase 3 Caspases / metabolism Cell Hypoxia / drug effects, physiology Enzyme Activation / drug effects Glucose / deficiency, metabolism Isoenzymes / antagonists & inhibitors, metabolism JNK Mitogen-Activated Protein Kinases L-Lactate Dehydrogenase / metabolism Mitogen-Activated Protein Kinase 1 / drug effects, metabolism Mitogen-Activated Protein Kinase 11 Mitogen-Activated Protein Kinase 14 Mitogen-Activated Protein Kinases / antagonists & inhibitors*, metabolism Models, Biological Nerve Growth Factor / pharmacology*, therapeutic use Neuroprotective Agents / pharmacology*, therapeutic use PC12 Cells Rats Reperfusion Injury / drug therapy, enzymology p38 Mitogen-Activated Protein Kinases |
| Chemical | |
Reg. No./Substance:
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0/Isoenzymes; 0/Neuroprotective Agents; 50-99-7/Glucose; 9061-61-4/Nerve Growth Factor; EC 1.1.1.27/L-Lactate Dehydrogenase; EC 2.7.11.24/JNK Mitogen-Activated Protein Kinases; EC 2.7.11.24/Mitogen-Activated Protein Kinase 1; EC 2.7.11.24/Mitogen-Activated Protein Kinase 11; EC 2.7.11.24/Mitogen-Activated Protein Kinase 14; EC 2.7.11.24/Mitogen-Activated Protein Kinases; EC 2.7.11.24/p38 Mitogen-Activated Protein Kinases; EC 3.4.22.-/Casp3 protein, rat; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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