Nitric oxide mediated induction of cytochrome c oxidase mRNA and protein in a mouse macrophage cell line

Joshua E. Lehrer-Graiwer, Bonnie L. Firestein, David S. Bredt

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16 Scopus citations


Neurons that express neuronal nitric oxide synthase (nNOS) are selectively spared from nitric oxide (NO)-induced cytotoxicity in acute cerebral ischemia and neurodegenerative conditions but the mechanism of this resistance is unknown. To identify specific gene products which may mediate this resistance, we performed polymerase chain reaction (PCR)-based subtractive hybridization on a mouse macrophage cell line treated with either L-NG-nitroarginine methyl ester (L-NAME, 1 mM, 1 h), an inhibitor of NOS, or with diethylamine NONOate (DEA NONO, 200 μM, 1 h), an NO donor. NO-treated cultures showed an acute induction of mRNA (less than 1 h after treatment) and protein (15 min) for the mitochondrial enzyme cytochrome c oxidase (CcO) as shown by Northern or Western blot analysis, respectively. Cytochrome c oxidase activity assay showed constant activity in NO-treated cultures, as compared to L-NAME-treated cultures. NO directly inhibits CcO, the terminal electron acceptor in mitochondrial oxidative respiration. Up-regulation of this enzyme by NO, therefore, appears to maintain vital CcO activity and cellular energy stores, thus contributing to selective sparing of nNOS neurons. Copyright (C) 2000 Elsevier Science Ireland Ltd.

Original languageEnglish (US)
Pages (from-to)107-110
Number of pages4
JournalNeuroscience Letters
Issue number2
StatePublished - Jul 14 2000
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • General Neuroscience


  • Apoptosis
  • Cytochrome c oxidase
  • Mitochondria
  • Neurotoxicity
  • Nitric oxide


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