A Functional Role of the Cyclin-Dependent Kinase Inhibitor 1 (P21WAF1/CIP1) for Neuronal Preconditioning. Issue 3 (March 2013)

• Record Type: Journal Article
• Authors: Mergenthaler, Philipp; Muselmann, Claudia; Sünwoldt, Juliane; Isaev, Nickolay K; Wieloch, Tadeusz; Dirnagl, Ulrich; Meisel, Andreas; Ruscher, Karsten
• Is Part Of: Journal of cerebral blood flow & metabolism. Volume 33:Issue 3(2013)
• Page Start: 351
• Page End: 355
• Publication Date: 2013-03
• Subjects: cyclin-dependent kinase inhibitor 1 (p21WAF1/CIP1) -- erythropoietin -- hypoxia -- ischemia -- HIF-1 target genes -- preconditioning; Cerebral circulation -- Periodicals; Brain -- Metabolism -- Periodicals; Brain -- Blood-vessels -- Periodicals; Cerebrovascular disease -- Periodicals; 612.824
• DOI: 10.1038/jcbfm.2012.213
• Languages: English
• ISSNs: 0271-678X

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.