Effect of nitric oxide on heme metabolism in pulmonary artery endothelial cells

Emily L. Yee, Bruce R. Pitt*, Timothy R. Billiar, Young Myeong Kim

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

77 Scopus citations


Primary intracellular targets for nitric oxide (NO) include nonheme iron-containing enzymes and protein-bound iron. Because NO is an important effector molecule in lung inflammation and endothelial cell-associated iron is critical to numerous forms of oxidant-mediated lung injury, we studied the effects of the NO donor S-nitrosoacetylpenicillamine (SNAP) on heme and iron metabolism in cultured sheep pulmonary artery endothelial cells. SNAP (300 μM) caused a transient increase in heme oxygenase-1 (HO-1) mRNA associated with a fivefold increase in HO activity that was completely blocked by the competitive HO inhibitor, tin protoporphyrin IX (SnPP). SNAP- induced activation of HO caused SnPP-sensitive reduction of activity of the hemoprotein catalase and decrease in heme iron. SNAP caused increases in iron-responsive gene products, ferritin and mitochondrial aconitase, secondary to the release of iron from heme stores via HO induction, since these changes were also sensitive to SnPP. The NO-induced increase in nonheme iron was apparent via electron paramagnetic resonance, where an enhanced SNAP-induced (300 μM for 4 h) g - 2.04 signal (e.g., dinitrosyl- iron-sulfur complex) was noted after exposure to a dose of SNAP (200 μM for 14 h) that in itself did not produce a detectable signal. These data show that exposure of pulmonary endothelial cells to NO results in profound changes in intracellular heme- and nonheme-iron homeostasis and that HO plays a central role in affecting this balance.

Original languageEnglish
Pages (from-to)L512-L518
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Issue number4 15-4
StatePublished - Oct 1996
Externally publishedYes


  • aconitase
  • catalase
  • ferritin
  • heme oxygenase
  • iron
  • tin protoporphyrin


Dive into the research topics of 'Effect of nitric oxide on heme metabolism in pulmonary artery endothelial cells'. Together they form a unique fingerprint.

Cite this