Document Detail

Stimulation of p42 and p44 mitogen-activated protein kinases by reactive oxygen species and nitric oxide in hippocampus.
MedLine Citation:
PMID:  9489720     Owner:  NLM     Status:  MEDLINE    
Reactive oxygen species (ROS) have been suggested to act as cellular messengers that mediate signal transduction cascades in various cell types. However, little is known about their role in this capacity in the nervous system. We have begun to investigate the role of ROS, and that of nitric oxide (NO), in mediating mitogen-activated protein kinase (MAPK) signaling in rat hippocampal slices. Our studies have revealed that direct exposure of hippocampal slices to hydrogen peroxide, xanthine/xanthine oxidase (a superoxide-generating system), sodium nitroprusside (an NO donor compound), S-nitroso-N-acetylpenicillamine (an NO donor compound), or 3-morpholinosydnonimine (a compound that produces NO and superoxide) results in an enhancement in tyrosine phosphorylation of several proteins, including proteins with apparent molecular masses of 42 and 44 kDa. We investigated the possibility that these proteins correspond to the active forms of p42 MAPK and p44 MAPK. Hippocampal slices exposed to various ROS and NO donors resulted in increases in levels of the active forms of both p42 MAPK and p44 MAPK. The ROS- and NO-enhanced tyrosine phosphorylation and activation of p42 MAPK and p44 MAPK were inhibited by pretreatment with the antioxidant N-acetyl-L-cysteine. Our observations indicate that ROS and NO can mediate protein tyrosine phosphorylation and MAPK signaling in the hippocampus via a redox-sensitive mechanism and suggest a potential cellular mechanism for their effects in the nervous system.
B I Kanterewicz; L T Knapp; E Klann
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of neurochemistry     Volume:  70     ISSN:  0022-3042     ISO Abbreviation:  J. Neurochem.     Publication Date:  1998 Mar 
Date Detail:
Created Date:  1998-03-12     Completed Date:  1998-03-12     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  2985190R     Medline TA:  J Neurochem     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1009-16     Citation Subset:  IM    
Department of Neuroscience and Center for the Neural Basis of Cognition, University of Pittsburgh, Pennsylvania 15260, USA.
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MeSH Terms
Acetylcysteine / pharmacology
Antioxidants / pharmacology
Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
Enzyme Activation
Free Radical Scavengers / pharmacology
Hippocampus / drug effects,  enzymology*
Hydrogen Peroxide / pharmacology
Mitogen-Activated Protein Kinase 1 / metabolism*
Mitogen-Activated Protein Kinase 3
Mitogen-Activated Protein Kinases*
Nitric Oxide / metabolism*
Organ Culture Techniques
Rats, Sprague-Dawley
Reactive Oxygen Species / metabolism*
Tyrosine / metabolism
Grant Support
Reg. No./Substance:
0/Antioxidants; 0/Free Radical Scavengers; 0/Reactive Oxygen Species; 10102-43-9/Nitric Oxide; 55520-40-6/Tyrosine; 616-91-1/Acetylcysteine; 7722-84-1/Hydrogen Peroxide; EC Protein Kinases; EC Protein Kinase 1; EC Protein Kinase 3; EC Protein Kinases

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