PMID- 12169577
OWN - NLM
STAT- MEDLINE
DCOM- 20020917
LR  - 20200930
IS  - 1040-0605 (Print)
IS  - 1040-0605 (Linking)
VI  - 283
IP  - 3
DP  - 2002 Sep
TI  - Elevated expression of hexokinase II protects human lung epithelial-like A549 
      cells against oxidative injury.
PG  - L573-84
AB  - Increased glucose utilization and hexokinase (HK)-II expression are adaptive 
      features of lung cells exposed to hypoxia or hyperoxia. HK-II is the most 
      regulated isoform of HK. Whether its overexpression could be protective against 
      oxidative stress was explored in human lung epithelial-like (A549) cells. HK-II 
      was overexpressed in A549 cells in a tetracycline-repressible retroviral vector 
      system. Elevated expression of HK-II was confirmed by Western blot and activity 
      measurements. Cell death caused by exposure to hyperoxia was decreased in 
      HK-II-overexpressing cells. This effect was reversed when HK-II expression was 
      suppressed with doxycycline. A similar protective effect was observed in 
      HK-II-overexpressing cells after treatment with 1 mM hydrogen peroxide for 48 h. 
      At baseline, fluorescence microscopy showed that overexpressed HK-II was 
      localized to mitochondria. Electron microscopic studies showed that 
      hyperoxia-exposed HK-II overexpressors had better-preserved and quantitatively 
      smaller mitochondria than those in which the HK-II expression was suppressed or 
      in the nontransduced A549 cells. Mitochondrial membrane potential was increased 
      in HK-II-overexpressing cells exposed to hyperoxia compared with the 
      nontransduced control cells under similar conditions. The present study 
      demonstrates that HK-II protects human lung epithelial-like A549 cells against 
      oxidative insults by protecting the mitochondria.
FAU - Ahmad, Aftab
AU  - Ahmad A
AD  - Department of Pediatrics, National Jewish Medical and Research Center, Denver, 
      Colorado 80206, USA.
FAU - Ahmad, Shama
AU  - Ahmad S
FAU - Schneider, B Kelly
AU  - Schneider BK
FAU - Allen, Corrie B
AU  - Allen CB
FAU - Chang, Ling-Yi
AU  - Chang LY
FAU - White, Carl W
AU  - White CW
LA  - eng
GR  - HL-52732/HL/NHLBI NIH HHS/United States
GR  - HL-56263/HL/NHLBI NIH HHS/United States
PT  - Journal Article
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 (Oxidants)
RN  - BBX060AN9V (Hydrogen Peroxide)
RN  - EC 2.7.1.1 (Hexokinase)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Cell Line
MH  - Cell Survival/drug effects/physiology
MH  - *Cytoprotection
MH  - Fluorescent Antibody Technique
MH  - Glucose/metabolism
MH  - Hexokinase/*metabolism
MH  - Humans
MH  - Hydrogen Peroxide/pharmacology
MH  - Hyperoxia/*metabolism/*pathology/physiopathology
MH  - Lung/drug effects/*metabolism/*pathology/physiopathology
MH  - Membrane Potentials/drug effects
MH  - Mitochondria/physiology
MH  - Oxidants/pharmacology
MH  - Staining and Labeling
EDAT- 2002/08/10 10:00
MHDA- 2002/09/18 10:01
CRDT- 2002/08/10 10:00
PHST- 2002/08/10 10:00 [pubmed]
PHST- 2002/09/18 10:01 [medline]
PHST- 2002/08/10 10:00 [entrez]
AID - 10.1152/ajplung.00410.2001 [doi]
PST - ppublish
SO  - Am J Physiol Lung Cell Mol Physiol. 2002 Sep;283(3):L573-84. doi: 
      10.1152/ajplung.00410.2001.