Nitric oxide mediates increased susceptibility to dopaminergic damage in Nurr1 heterozygous mice

Syed Z. Imam, Joseph Jankovic, Syed F. Ali, John T. Skinner, Wenjie Xie, Orla M. Conneely, Weidong Le

Research output: Contribution to journalArticlepeer-review

26 Scopus citations


Knocking out of Nurr1 gene, a member of nuclear receptor superfamily, causes selective agenesis of dopaminergic neurons in midbrain. Reduced expression of Nurr1 increases the vulnerability of mesencephalic dopamine neurons to dopaminergic toxins. We evaluated the role of nitric oxide as a possible mechanism for this increased susceptibility. Increased expression of neuronal nitric oxide synthase and increased 3-nitrotyrosine were observed in striatum of Nurr1 heterozygous (Nurr1 +/ -) mice as compared with wild-type. Increased cytochrome C activation and consecutive release of Smac/DIABLO were also observed in Nurr1 +/- mice. An induction of active Caspase-3 and p53, cleavage of poly-ADP (RNase) polymerase and reduced expression of bcl-Z were observed in Nurr1 +/- mice. Methamphetamine significantly increased these markers in Nurr1 +/- mice as compared with wild-type. The present data therefore suggest that nitric oxide plays a role as a modulating factor for the increased susceptibility, but not the potentiation, of the dopaminergic terminals in Nurr1 +/- mice. We also report that this increased neuronal nitric oxide synthase expression and increased nitration in Nurr1 +/- mice led to the activation of apoptotic cascade via the differential alterations in the DNA binding activity of transcription factors responsible for the propagation of growth arrest as well as apoptosis.

Original languageEnglish (US)
Pages (from-to)1441-1450
Number of pages10
JournalFASEB Journal
Issue number11
StatePublished - Sep 2005


  • 3-NT
  • Apoptosis
  • Caspase
  • Dopamine
  • Nitric oxide
  • Transcription

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology


Dive into the research topics of 'Nitric oxide mediates increased susceptibility to dopaminergic damage in Nurr1 heterozygous mice'. Together they form a unique fingerprint.

Cite this