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

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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; Dirnagl, Ulrich; Meisel, Andreas; Ruscher, Karsten.

I: Journal of Cerebral Blood Flow and Metabolism, Vol. 33, Nr. 3, 2013, s. 351-355.

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Mergenthaler, Philipp ; Muselmann, Claudia ; Suenwoldt, Juliane ; Isaev, Nickolay K. ; Wieloch, Tadeusz ; Dirnagl, Ulrich ; Meisel, Andreas ; Ruscher, Karsten. / A functional role of the cyclin-dependent kinase inhibitor 1 (p21(WAF1/CIP1)) for neuronal preconditioning. I: Journal of Cerebral Blood Flow and Metabolism. 2013 ; Vol. 33, Nr. 3. s. 351-355.

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TY - JOUR

T1 - A functional role of the cyclin-dependent kinase inhibitor 1 (p21(WAF1/CIP1)) for neuronal preconditioning

AU - Mergenthaler, Philipp

AU - Muselmann, Claudia

AU - Suenwoldt, Juliane

AU - Isaev, Nickolay K.

AU - Wieloch, Tadeusz

AU - Dirnagl, Ulrich

AU - Meisel, Andreas

AU - Ruscher, Karsten

N1 - 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)

PY - 2013

Y1 - 2013

N2 - 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

AB - 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

KW - cyclin-dependent kinase inhibitor 1 (p21(WAF1/CIP1))

KW - erythropoietin

KW - hypoxia

KW - ischemia

KW - HIF-1 target genes

KW - preconditioning

U2 - 10.1038/jcbfm.2012.213

DO - 10.1038/jcbfm.2012.213

M3 - Article

C2 - 23299246

VL - 33

SP - 351

EP - 355

JO - Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism

JF - Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism

SN - 1559-7016

IS - 3

ER -