title: A functional role of the cyclin-dependent kinase inhibitor 1 (p21(WAF1/CIP1)) for neuronal preconditioning.
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.
authors.affiliation: Department of Experimental Neurology, Charitéplatz, Berlin, Germany.
authors.forename: Philipp
authors.initials: P
authors.lastname: Mergenthaler
authors.forename: Claudia
authors.initials: C
authors.lastname: Muselmann
authors.forename: Juliane
authors.initials: J
authors.lastname: Sünwoldt
authors.forename: Nickolay K
authors.initials: NK
authors.lastname: Isaev
authors.forename: Tadeusz
authors.initials: T
authors.lastname: Wieloch
authors.forename: Ulrich
authors.initials: U
authors.lastname: Dirnagl
authors.forename: Andreas
authors.initials: A
authors.lastname: Meisel
authors.forename: Karsten
authors.initials: K
authors.lastname: Ruscher
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects / Q000235:genetics; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000096:biosynthesis* / Q000235:genetics; D003676:Deferoxamine / Q000494:pharmacology; D004921:Erythropoietin / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D002534:Hypoxia, Brain / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051793:Hypoxia-Inducible Factor 1 / Q000235:genetics / Q000378:metabolism; D019194:Ischemic Preconditioning; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D017262:Siderophores / Q000494:pharmacology
chemical_list: C493957:Cdkn1a protein, mouse; D050759:Cyclin-Dependent Kinase Inhibitor p21; D051793:Hypoxia-Inducible Factor 1; D009419:Nerve Tissue Proteins; D017262:Siderophores; D004921:Erythropoietin; D003676:Deferoxamine