Polyamine regulatory processes and oxidative stress in monocrotaline-treated pulmonary artery endothelial cells

Shewan M. Aziz, Michal Toborek, Bernhard Hennig, Eric Endean, David W. Lipke

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Alterations in polyamine metabolism may be a critical mechanism of monocrotaline (MCT)-induced structural remodeling of the pulmonary vasculature. In the present study, the hypothesis that MCT, through the induction of oxidative stress, modulates cellular polyamine regulatory mechanisms which in turn might be involved in the upregulation of fibronectin production in pulmonary artery endothelial cells (PAEC) was examined. A 24-h treatment with MCT significantly increased PAEC polyamine concentrations as compared to vehicle-treated cells. In addition, exposure to MCT caused an increase in abundance of ornithine decarboxylase (ODC mRNA upregulation of ODC activity and enhancement of spermidine import into PAEC. Inhibition of de novo polyamine synthesis further increased spermidine uptake in MCT-treated cells. The depletion of cellular polyamine contents through the blockade of both de novo polyamine biosynthesis and polyamine transport prevented MCT-induced increases in the medium level of fibronectin. In addition, PAEC treatment with MCT stimulated cellular oxidative stress as determined by increased levels of thiobarbituric acid reactive substances, enhanced dichlorofluorescein fluorescence and activation of NF-κB. A co-treatment with dimethylthiourea, an oxygen radical scavenger, prevented MCT-induced increases in cellular oxidation and attenuated disturbances in polyamine metabolism. These data suggest that MCT can stimulate polyamine regulatory processes in PAEC possibly through an increase in cellular oxidative stress. The present study may have significant implication in understanding mechanisms of MCT-induced pulmonary hypertension and remodeling of pulmonary vasculature.

Original languageEnglish (US)
Pages (from-to)801-812
Number of pages12
JournalCell Biology International
Volume21
Issue number12
DOIs
StatePublished - Dec 1997
Externally publishedYes

Keywords

  • Endothelial cells
  • Monocrotaline
  • Oxidative stress
  • Polyamine synthesis
  • Polyamine transport

ASJC Scopus subject areas

  • Cell Biology

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