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Inhibitory effect of zinc on hypoxic HIF-1 activation in astrocytes

Authors
 Insook Kim  ;  Chul Hoon Kim  ;  Gi Ho Seo  ;  Hyun Soo Kim  ;  Jinu Lee  ;  Dong Goo Kim  ;  Young Soo Ahn 
Citation
 NEUROREPORT, Vol.19(10) : 1063-1066, 2008 
Journal Title
 NEUROREPORT 
ISSN
 0959-4965 
Issue Date
2008
MeSH
Antineoplastic Agents/pharmacology ; Astrocytoma/pathology ; Cell Line ; Tumor ; Cell Nucleus/metabolism ; Dose-Response Relationship ; Drug ; Drug Interactions ; Electrophoretic Mobility Shift Assay/methods ; Erythropoietin/genetics ; Erythropoietin/metabolism ; Gene Expression Regulation ; Neoplastic/drug effects* ; Humans ; Hypoxia/metabolism* ; Hypoxia-Inducible Factor 1 ; alpha Subunit/metabolism* ; Proline/analogs & derivatives ; Proline/pharmacology ; Protein Transport/drug effects ; Thiocarbamates/pharmacology ; Time Factors ; Zinc Sulfate/pharmacokinetics* ; Zinc Sulfate/pharmacology
Keywords
astrocytes ; erythropoietin ; hypoxia ; hypoxia-inducible factor-1 ; zinc
Abstract
Hypoxia-inducible factor-1 (HIF-1) regulates the expression of neuroprotective genes such as erythropoietin (EPO). We investigated the mechanism by which zinc, an excitotoxin-like metal, regulates HIF-1 under hypoxic conditions in astrocytes. In hypoxic LN215 cells, HIF-1alpha stabilized and accumulated in the nucleus, resulting in an increase in its DNA-binding activity to the EPO enhancer. Zinc inhibited hypoxia-induced increases in HIF-1 DNA-binding activity and the HIF-1-dependent mRNA expression of EPO. Zinc did not affect hypoxic stabilization of HIF-1alpha. Nuclear migration of HIF-1alpha upon hypoxia was reduced by zinc. Complete blockade of hypoxia-induced assembly of HIF-1alpha-HIF-1beta complex was observed after treatment of zinc. These findings suggest that zinc hampers hypoxia-stimulated HIF-1 activation in astrocytes by inhibiting nuclear HIF-1alpha translocation and subsequently disrupting HIF-1 heterodimerization
Full Text
http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&AN=00001756-200807020-00013&LSLINK=80&D=ovft
DOI
10.1097/WNR.0b013e328304d9ac
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers
Yonsei Authors
Kim, Dong Goo(김동구)
Kim, In Sook(김인숙)
Kim, Chul Hoon(김철훈) ORCID logo https://orcid.org/0000-0002-7360-429X
Ahn, Young Soo(안영수)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/106219
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