Elevated expression of hexokinase II protects human lung epithelial-like A549 cells against oxidative injury.

Academic Article


  • 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.
  • Keywords

  • Cell Line, Cell Survival, Cytoprotection, Fluorescent Antibody Technique, Glucose, Hexokinase, Humans, Hydrogen Peroxide, Hyperoxia, Lung, Membrane Potentials, Mitochondria, Oxidants, Staining and Labeling
  • Digital Object Identifier (doi)

    Author List

  • Ahmad A; Ahmad S; Schneider BK; Allen CB; Chang L-Y; White CW
  • Start Page

  • L573
  • End Page

  • L584
  • Volume

  • 283
  • Issue

  • 3