Nitric oxide and peroxynitrite-mediated pulmonary cell death

Andrew J. Gow, Stephen R. Thom, Harry Ischiropoulos

Research output: Contribution to journalArticle

84 Citations (Scopus)

Abstract

Nitric oxide (·NO) can be produced within the lung, and recently inhaled nitric oxide has been used as a therapeutic agent. Peroxynitrite1 (ONOO-), the product of the nearly diffusion-limited reaction between ·NO and superoxide, may represent the proximal reactive species mediating ·NO injury to pulmonary cells. To investigate the physiological and pathological reactivities of ·NO and ONOO- at the molecular and cellular levels, bovine pulmonary artery endothelial cells (BPAEC) and rat type II epithelial cells were exposed to ·NO (0.01-2.5 μM/min for 2 h) generated by spermine- NONOate and papa-NONOate and to the same fluxes of ONOO- generated by 1,3- morpholinosydnonimine (SIN-1). Exposure to SIN-1 resulted in cellular injury and death in both cell types. Epithelial cells displayed a concentration- dependent loss of cellular viability within 8 h of exposure. In contrast, BPAEC loss of cellular viability was evident after 18 h postexposure. Events preceding cell death in BPAEC include depolarization of the mitochondrial membrane, evident as early as 6 h postexposure, loss of cellular redox activity at 16 h, and DNA fragmentation detected by in situ staining at 18 h after exposure. Exposure of BPAEC to ·NO did not affect the cellular viability, but type II cells were injured in a manner similar to ONOO- exposure. ·NO-mediated cellular injury within type II cells was reduced by preincubation with N-acetylcysteine. The data imply that the pathological and physiological effects of ·NO may be regulated by its reactions with superoxide and reduced thiols.

Original languageEnglish
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume274
Issue number1 18-1
Publication statusPublished - Jan 1998
Externally publishedYes

Fingerprint

Peroxynitrous Acid
Nitric Oxide
Cell Death
Lung
Pulmonary Artery
Endothelial Cells
Superoxides
Epithelial Cells
Wounds and Injuries
Acetylcysteine
Mitochondrial Membranes
Lung Injury
DNA Fragmentation
Sulfhydryl Compounds
Oxidation-Reduction
Cell Survival
Staining and Labeling

Keywords

  • Apoptosis
  • Endothelium
  • Superoxide
  • Type II epithelium

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Cell Biology
  • Physiology
  • Physiology (medical)

Cite this

Nitric oxide and peroxynitrite-mediated pulmonary cell death. / Gow, Andrew J.; Thom, Stephen R.; Ischiropoulos, Harry.

In: American Journal of Physiology - Lung Cellular and Molecular Physiology, Vol. 274, No. 1 18-1, 01.1998.

Research output: Contribution to journalArticle

Gow, Andrew J. ; Thom, Stephen R. ; Ischiropoulos, Harry. / Nitric oxide and peroxynitrite-mediated pulmonary cell death. In: American Journal of Physiology - Lung Cellular and Molecular Physiology. 1998 ; Vol. 274, No. 1 18-1.
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