Document Detail


A functional role of the cyclin-dependent kinase inhibitor 1 (p21(WAF1/CIP1)) for neuronal preconditioning.
MedLine Citation:
PMID:  23299246     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Hypoxic preconditioning is thought to rely on gene products regulated by hypoxia-inducible factor (HIF)-1. Here, we show that the HIF-1 target gene cyclin-dependent kinase inhibitor 1, p21(WAF1/CIP1), is essential for neuroprotection by hypoxic/aglycemic or erythropoietin preconditioning using wild-type and p21(WAF1/CIP1)-deficient neurons. Furthermore, overexpression of wild-type p21(WAF1/CIP1) or phospho-mutants significantly increased cell death after hypoxia/aglycemia. Moreover, deferoxamine-induced endogenous tolerance did not involve p21(WAF1/CIP1) expression in cortical neurons. Our data suggest that balanced expression and potentially posttranslational regulation of p21(WAF1/CIP1) is required for hypoxic preconditioning.
Authors:
Philipp Mergenthaler; Claudia Muselmann; Juliane Sünwoldt; Nickolay K Isaev; Tadeusz Wieloch; Ulrich Dirnagl; Andreas Meisel; Karsten Ruscher
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2013-01-09
Journal Detail:
Title:  Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism     Volume:  33     ISSN:  1559-7016     ISO Abbreviation:  J. Cereb. Blood Flow Metab.     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-03-01     Completed Date:  2013-04-19     Revised Date:  2014-03-07    
Medline Journal Info:
Nlm Unique ID:  8112566     Medline TA:  J Cereb Blood Flow Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  351-5     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Death / drug effects,  genetics
Cyclin-Dependent Kinase Inhibitor p21 / biosynthesis*,  genetics
Deferoxamine / pharmacology
Erythropoietin / pharmacology
Gene Expression Regulation / drug effects,  genetics
Hypoxia, Brain / genetics,  metabolism*,  pathology
Hypoxia-Inducible Factor 1 / genetics,  metabolism
Ischemic Preconditioning*
Mice
Mice, Knockout
Mutation
Nerve Tissue Proteins / biosynthesis*,  genetics
Siderophores / pharmacology
Chemical
Reg. No./Substance:
0/Cdkn1a protein, mouse; 0/Cyclin-Dependent Kinase Inhibitor p21; 0/Hypoxia-Inducible Factor 1; 0/Nerve Tissue Proteins; 0/Siderophores; 11096-26-7/Erythropoietin; J06Y7MXW4D/Deferoxamine
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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