PMID- 10666126
OWN - NLM
STAT- MEDLINE
DCOM- 20000331
LR  - 20200930
IS  - 1040-0605 (Print)
IS  - 1040-0605 (Linking)
VI  - 278
IP  - 2
DP  - 2000 Feb
TI  - Hypoxia induces hexokinase II gene expression in human lung cell line A549.
PG  - L407-16
AB  - During adaptation to hypoxic and hyperoxic conditions, the genes involved in 
      glucose metabolism are upregulated. To probe involvement of the transcription 
      factor hypoxia-induced factor-1 (HIF-1) in hexokinase (HK) II expression in human 
      pulmonary cells, A549 cells and small-airway epithelial cells (SAECs) were 
      exposed to stimuli such as hypoxia, deferoxamine (DFO), and metal ions. The 
      largest increase in HK-II (20-fold for mRNA and 2.5-fold for enzymatic activity) 
      was observed in A549 cells when exposed to DFO. All stimuli selectively increased 
      the 5.5-kb rather than 4-kb transcript in A549 cells. Cycloheximide and 
      actinomycin D inhibited these responses. In addition, cells were transfected with 
      luciferase reporter constructs driven by the full-length HK-II 5'-regulatory 
      region (4.0 kb) or various deletions of that region. A549 cells transfected with 
      the 4.0-kb construct and exposed to hypoxia or DFO increased their luciferase 
      activity 7- and 10-fold, respectively, indicating that HK-II induction is, at 
      least in part, due to increased gene transcription. Sixty percent of the 
      inducible activity of the 4.0-kb construct was shown to reside within the 
      proximal 0.5 kb. Additionally, cotransfection with a stable HIF-1 mutant and the 
      4.0-kb promoter construct resulted in increased luciferase activity under 
      normoxic conditions. These results strongly suggest that HK-II is selectively 
      regulated in pulmonary cells by a HIF-1-dependent mechanism.
FAU - Riddle, S R
AU  - Riddle SR
AD  - Department of Pediatrics, National Jewish Medical and Research Center, Denver, 
      Colorado 80206, USA.
FAU - Ahmad, A
AU  - Ahmad A
FAU - Ahmad, S
AU  - Ahmad S
FAU - Deeb, S S
AU  - Deeb SS
FAU - Malkki, M
AU  - Malkki M
FAU - Schneider, B K
AU  - Schneider BK
FAU - Allen, C B
AU  - Allen CB
FAU - White, C W
AU  - White CW
LA  - eng
GR  - HL52732/HL/NHLBI NIH HHS/United States
GR  - HL56263/HL/NHLBI NIH HHS/United States
GR  - HL57144/HL/NHLBI NIH HHS/United States
GR  - etc.
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Am J Physiol Lung Cell Mol Physiol
JT  - American journal of physiology. Lung cellular and molecular physiology
JID - 100901229
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (HIF1A protein, human)
RN  - 0 (Hypoxia-Inducible Factor 1)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Nucleic Acid Synthesis Inhibitors)
RN  - 0 (Protein Synthesis Inhibitors)
RN  - 0 (RNA, Messenger)
RN  - 0 (Transcription Factors)
RN  - EC 1.13.12.- (Luciferases)
RN  - EC 2.7.1.1 (Hexokinase)
RN  - J06Y7MXW4D (Deferoxamine)
SB  - IM
MH  - Cell Line
MH  - DNA-Binding Proteins/pharmacology
MH  - Deferoxamine/pharmacology
MH  - *Gene Expression
MH  - Hexokinase/*genetics
MH  - Humans
MH  - Hypoxia/*enzymology/*genetics
MH  - Hypoxia-Inducible Factor 1
MH  - Hypoxia-Inducible Factor 1, alpha Subunit
MH  - Luciferases/metabolism
MH  - Lung/*enzymology/pathology
MH  - Nuclear Proteins/pharmacology
MH  - Nucleic Acid Synthesis Inhibitors/pharmacology
MH  - Promoter Regions, Genetic/genetics
MH  - Protein Synthesis Inhibitors/pharmacology
MH  - RNA, Messenger/metabolism
MH  - Respiratory System/enzymology/pathology
MH  - *Transcription Factors
MH  - Transfection
EDAT- 2000/02/09 00:00
MHDA- 2000/02/09 00:01
CRDT- 2000/02/09 00:00
PHST- 2000/02/09 00:00 [pubmed]
PHST- 2000/02/09 00:01 [medline]
PHST- 2000/02/09 00:00 [entrez]
AID - 10.1152/ajplung.2000.278.2.L407 [doi]
PST - ppublish
SO  - Am J Physiol Lung Cell Mol Physiol. 2000 Feb;278(2):L407-16. doi: 
      10.1152/ajplung.2000.278.2.L407.