Synergistic cytotoxicity from nitric oxide and hyperoxia in cultured lung cells

The American Journal of Physiology
P NarulaS Horowitz

Abstract

Exogenous nitric oxide (NO) is being tested clinically for the treatment of pulmonary hypertension in infants and children. In most cases, these patients receive simultaneous oxygen (O2) therapy. However, little is known about the combined toxicity of NO + hyperoxia. To test this potential toxicity, human alveolar epithelial cells (A549 cells) and human lung microvascular endothelial lung cells were cultured in room air (control), hyperoxia (95% O2), NO (derived from chemical donors), or combined hyperoxia + NO. Control cells grew normally over a 6-day study period. In contrast, cell death from hyperoxia was evident after 4-5 days, whereas cells neither died nor divided in NO alone. However, cells exposed to both NO and hyperoxia began to die on day 2 and died rapidly thereafter. This cytotoxic effect was clearly synergistic, and cell death did not occur via apoptosis. As an indicator of peroxynitrite formation, nitrotyrosine-containing proteins were assayed using anti-nitrotyrosine antibodies. Two protein bands, at molecular masses of 25 and 35 kDa, were found to be increased in A549 cells exposed to NO or NO + hyperoxia. These results indicate that combined NO + hyperoxia has a synergistic cytotoxic effect on alveolar epithel...Continue Reading

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Citations

Jul 5, 2003·American Journal of Respiratory Cell and Molecular Biology·Yuchi LiJeffrey A Kazzaz
Jun 1, 2004·American Journal of Physiology. Lung Cellular and Molecular Physiology·Loretta Sparkman, Vijayakumar Boggaram
Dec 13, 2006·American Journal of Physiology. Lung Cellular and Molecular Physiology·Deepika JainMichael F Beers
Aug 5, 2003·American Journal of Physiology. Lung Cellular and Molecular Physiology·Darrell SalinasVijayakumar Boggaram
Jan 24, 2003·American Journal of Respiratory Cell and Molecular Biology·Shama AhmadCarl W White

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