Nitric oxide and peroxynitrite-mediated pulmonary cell death

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

Research output: Contribution to journalArticle

85 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

Keywords

  • Apoptosis
  • Endothelium
  • Superoxide
  • Type II epithelium

ASJC Scopus subject areas

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

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