Overexpression of heme oxygenase-1 in human pulmonary epithelial cells results in cell growth arrest and increased resistance to hyperoxia. Academic Article uri icon

Overview

MeSH

  • Animals
  • Blotting, Northern
  • Cell Division
  • Cell Survival
  • DNA Probes
  • DNA, Complementary
  • Epithelial Cells
  • Epithelium
  • Flow Cytometry
  • Humans
  • Isoenzymes
  • Kinetics
  • Lung Neoplasms
  • Oxygen
  • RNA, Messenger
  • Rats
  • Recombinant Proteins
  • Transfection
  • Tumor Cells, Cultured

MeSH Major

  • Cell Cycle
  • Heme Oxygenase (Decyclizing)
  • Transcription, Genetic

abstract

  • Heme oxygenase (HO) catalyzes the rate-limiting step in the degradation of heme to biliverdin, which is reduced by biliverdin reductase to bilirubin. Heme oxygenase-1 (HO-1) is inducible not only by its heme substrate, but also by a variety of agents causing oxidative stress. Although much is known about the regulation of HO-1 expression, the functional significance of HO-1 induction after oxidant insult is still poorly understood. We hypothesize and provide evidence that HO-1 induction serves to protect cells against oxidant stress. Human pulmonary epithelial cells (A549 cells) stably transfected with the rat HO-1 cDNA exhibit marked increases of HO-1 mRNA levels which were correlated with increased HO enzyme activity. Cells that overexpress HO-1 (A549-A4) exhibited a marked decrease in cell growth compared with wild-type A549 (A549-WT) cells or A549 cells transfected with control DNA (A549-neo). This slowing of cell growth was associated with an increased number of cells in G0/G1 phase during the exponential growth phase and decreased entry into the S phase, as determined by flow cytometric analysis of propidium iodide-stained cells and pulse experiments with bromodeoxyuridine. Furthermore, the A549-A4 cells accumulated at the G2/M phase and failed to progress through the cell cycle when stimulated with serum, whereas the A549-neo control cells exhibited normal cell cycle progression. Interestingly, the A549-A4 cells also exhibited marked resistance to hyperoxic oxidant insult. Tin protoporphyrin, a selective inhibitor of HO, reversed the growth arrest and ablated the increased survival against hyperoxia observed in the A549-A4 cells overexpressing HO-1. Taken together, our data suggest that overexpression of HO-1 results in cell growth arrest, which may facilitate cellular protection against non-heme-mediated oxidant insult such as hyperoxia.

publication date

  • September 17, 1996

has subject area

  • Animals
  • Blotting, Northern
  • Cell Cycle
  • Cell Division
  • Cell Survival
  • DNA Probes
  • DNA, Complementary
  • Epithelial Cells
  • Epithelium
  • Flow Cytometry
  • Heme Oxygenase (Decyclizing)
  • Humans
  • Isoenzymes
  • Kinetics
  • Lung Neoplasms
  • Oxygen
  • RNA, Messenger
  • Rats
  • Recombinant Proteins
  • Transcription, Genetic
  • Transfection
  • Tumor Cells, Cultured

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC38395

PubMed ID

  • 8816811

Additional Document Info

start page

  • 10393

end page

  • 10398

volume

  • 93

number

  • 19