Reactive oxygen and nitrogen species regulate inducible nitric oxide synthase function shifting the balance of nitric oxide and superoxide production

Jian Sun, Lawrence J. Druhan, Jay L. Zweier

Research output: Contribution to journalArticlepeer-review

Abstract

Inducible NOS (iNOS) is induced in diseases associated with inflammation and oxidative stress, and questions remain regarding its regulation. We demonstrate that reactive oxygen/nitrogen species (ROS/RNS) dose-dependently regulate iNOS function. Tetrahydrobiopterin (BH4)-replete iNOS was exposed to increasing concentrations of ROS/RNS and activity was measured with and without subsequent BH4 addition. Peroxynitrite (ONOO-) produced the greatest change in NO generation rate, ∼95% decrease, and BH4 only partially restored this loss of activity. Superoxide (O2-) greatly decreased NO generation, however, BH4 addition restored this activity. Hydroxyl radical (OH) mildly decreases NO generation in a BH4-dependent manner iNOS was resistant to H2O2 with only slightly decreased NO generation with up to millimolar concentrations. In contrast to the inhibition of NO generation, ROS enhanced O2.- production from iNOS, while ONOO- had the opposite effect. Thus, ROS promote reversible iNOS uncoupling, while ONOO- induces irreversible enzyme inactivation and decreases both NO and O2.- production.

Original languageEnglish (US)
Pages (from-to)130-137
Number of pages8
JournalArchives of Biochemistry and Biophysics
Volume494
Issue number2
DOIs
StatePublished - Feb 2010
Externally publishedYes

Keywords

  • Dose-dependent
  • Hydrogen peroxide
  • Hydroxyl radical
  • Inducible nitric oxide synthase
  • Monomerization
  • Nitric oxide
  • Peroxynitrite
  • Superoxide
  • Tetrahydrobiopterin
  • Uncoupling

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Fingerprint Dive into the research topics of 'Reactive oxygen and nitrogen species regulate inducible nitric oxide synthase function shifting the balance of nitric oxide and superoxide production'. Together they form a unique fingerprint.

Cite this