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A functional role of the cyclin-dependent kinase inhibitor 1 (p21(WAF1/CIP1)) for neuronal preconditioning

Mergenthaler, Philipp ; Muselmann, Claudia ; Suenwoldt, Juliane ; Isaev, Nickolay K. ; Wieloch, Tadeusz LU ; Dirnagl, Ulrich ; Meisel, Andreas and Ruscher, Karsten LU (2013) In Journal of Cerebral Blood Flow and Metabolism 33(3). p.351-355
Abstract
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. Journal of... (More)
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. Journal of Cerebral Blood Flow & Metabolism (2013) 33, 351-355; doi:10.1038/jcbfm.2012.213; published online 9 January 2013 (Less)
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author
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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
cyclin-dependent kinase inhibitor 1 (p21(WAF1/CIP1)), erythropoietin, hypoxia, ischemia, HIF-1 target genes, preconditioning
in
Journal of Cerebral Blood Flow and Metabolism
volume
33
issue
3
pages
351 - 355
publisher
Nature Publishing Group
external identifiers
  • wos:000315590200006
  • scopus:84874645218
  • pmid:23299246
ISSN
1559-7016
DOI
10.1038/jcbfm.2012.213
language
English
LU publication?
yes
additional info
The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Laboratory for Experimental Brain Research (013041000)
id
f1cfc3ce-8a1a-41b0-bfa4-5611ab5d5511 (old id 3670067)
date added to LUP
2016-04-01 12:59:50
date last changed
2022-02-26 18:44:26
@article{f1cfc3ce-8a1a-41b0-bfa4-5611ab5d5511,
  abstract     = {{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. Journal of Cerebral Blood Flow & Metabolism (2013) 33, 351-355; doi:10.1038/jcbfm.2012.213; published online 9 January 2013}},
  author       = {{Mergenthaler, Philipp and Muselmann, Claudia and Suenwoldt, Juliane and Isaev, Nickolay K. and Wieloch, Tadeusz and Dirnagl, Ulrich and Meisel, Andreas and Ruscher, Karsten}},
  issn         = {{1559-7016}},
  keywords     = {{cyclin-dependent kinase inhibitor 1 (p21(WAF1/CIP1)); erythropoietin; hypoxia; ischemia; HIF-1 target genes; preconditioning}},
  language     = {{eng}},
  number       = {{3}},
  pages        = {{351--355}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Journal of Cerebral Blood Flow and Metabolism}},
  title        = {{A functional role of the cyclin-dependent kinase inhibitor 1 (p21(WAF1/CIP1)) for neuronal preconditioning}},
  url          = {{http://dx.doi.org/10.1038/jcbfm.2012.213}},
  doi          = {{10.1038/jcbfm.2012.213}},
  volume       = {{33}},
  year         = {{2013}},
}