Document Detail


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.
MedLine Citation:
PMID:  14997018     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Rinat Tabakman; Hao Jiang; Erik Schaefer; Robert A Levine; Philip Lazarovici
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of molecular neuroscience : MN     Volume:  22     ISSN:  0895-8696     ISO Abbreviation:  J. Mol. Neurosci.     Publication Date:  2004  
Date Detail:
Created Date:  2004-03-03     Completed Date:  2004-06-17     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  9002991     Medline TA:  J Mol Neurosci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  237-50     Citation Subset:  IM    
Affiliation:
Department of Pharmacology and Experimental Therapeutics, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 91120, Israel.
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MeSH Terms
Descriptor/Qualifier:
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:
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

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