Mitochondrial localization and function of heme oxygenase-1 in cigarette smoke-induced cell death. Academic Article uri icon

Overview

MeSH

  • Adenosine Triphosphate
  • Animals
  • Cell Death
  • Cell Line
  • Epithelial Cells
  • Humans
  • Male
  • Membrane Potential, Mitochondrial
  • Mice
  • Mice, Inbred AKR
  • Respiratory Mucosa
  • Transfection
  • Up-Regulation

MeSH Major

  • Gene Expression Regulation, Enzymologic
  • Heme Oxygenase-1
  • Lung
  • Mitochondria
  • Smoke

abstract

  • Cigarette smoke-induced apoptosis and necrosis contribute to the pathogenesis of chronic obstructive pulmonary disease. The induction of heme oxygenase-1 provides cytoprotection against oxidative stress, and may protect in smoking-related disease. Since mitochondria regulate cellular death, we examined the functional expression and mitochondrial localization of heme oxygenase-1 in pulmonary epithelial cells exposed to cigarette smoke extract (CSE), and its role in modulating cell death. Heme oxygenase-1 expression increased dramatically in cytosolic and mitochondrial fractions of human alveolar (A549), or bronchial epithelial cells (Beas-2b) exposed to either hemin, lipopolysaccharide, or CSE. Mitochondrial localization of heme oxygenase-1 was also observed in a primary culture of human small airway epithelial cells. Furthermore, heme oxygenase activity increased dramatically in mitochondrial fractions, and in whole cell extracts of Beas-2b after exposure to hemin and CSE. The mitochondrial localization of heme oxygenase-1 in Beas-2b was confirmed using immunogold-electron microscopy and immunofluorescence labeling on confocal laser microscopy. CSE caused loss of cellular ATP and rapid depolarization of mitochondrial membrane potential. Apoptosis occurred in Beas-2b at low concentrations of cigarette smoke extract, whereas necrosis occurred at high concentrations. Overexpression of heme oxygenase-1 inhibited CSE-induced Beas-2b cell death and preserved cellular ATP levels. Finally, heme oxygenase-1 mRNA expression was elevated in the lungs of mice chronically exposed to cigarette smoke. We demonstrate the functional compartmentalization of heme oxygenase-1 in the mitochondria of lung epithelial cells, and its potential role in defense against mitochondria-mediated cell death during CSE exposure.

publication date

  • April 2007

has subject area

  • Adenosine Triphosphate
  • Animals
  • Cell Death
  • Cell Line
  • Epithelial Cells
  • Gene Expression Regulation, Enzymologic
  • Heme Oxygenase-1
  • Humans
  • Lung
  • Male
  • Membrane Potential, Mitochondrial
  • Mice
  • Mice, Inbred AKR
  • Mitochondria
  • Respiratory Mucosa
  • Smoke
  • Transfection
  • Up-Regulation

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC1899328

Digital Object Identifier (DOI)

  • 10.1165/rcmb.2006-0214OC

PubMed ID

  • 17079780

Additional Document Info

start page

  • 409

end page

  • 417

volume

  • 36

number

  • 4