Ni2+, a double-acting inhibitor of neuronal nitric oxide synthase interfering with L-arginine binding and Ca2+/calmodulin-dependent enzyme activation

Anna Palumbo, Giuseppe Astarita, Mauro Picardo, Marco D'Ischia

Research output: Contribution to journalArticlepeer-review

Abstract

Ni2+, a toxic and carcinogenic pollutant and one of the leading causes of contact dermatitis, is shown to inhibit neuronal nitric oxide synthase (nNOS) in a competitive, reversible manner with respect to the substrate L-arginine (Ki = 30 ± 4 μM). The IC50 values were dependent on calmodulin (CAM) concentration, but proved independent of Ca2+, tetrahydrobiopterin (BH4) and other essential cofactors. Ni2+ also inhibited CAM-dependent cytochrome c reduction, NADPH oxidation, and H2O2 production by nNOS. Overall, the action profile of Ni2+ was suggestive of an unusual, double-acting inhibitor of nNOS affecting L-arginine-binding and Ca2+/CAM-dependent enzyme activation.

Original languageEnglish
Pages (from-to)142-146
Number of pages5
JournalBiochemical and Biophysical Research Communications
Volume285
Issue number1
DOIs
Publication statusPublished - 2001

Keywords

  • Calmodulin
  • Neuronal nitric oxide synthase inhibition
  • Nickel ions

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

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