Nitric oxide induces hypoxia ischemic injury in the neonatal brain via the disruption of neuronal iron metabolism

Qing Lu, Valerie A. Harris, Ruslan Rafikov, Xutong Sun, Sanjiv Kumar, Stephen Matthew Black

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

We have recently shown that increased hydrogen peroxide (H2O2) generation is involved in hypoxia-ischemia (HI)-mediated neonatal brain injury. H2O2 can react with free iron to form the hydroxyl radical, through Fenton Chemistry. Thus, the objective of this study was to determine if there was a role for the hydroxyl radical in neonatal HI brain injury and to elucidate the underlying mechanisms. Our data demonstrate that HI increases the deposition of free iron and hydroxyl radical formation, in both P7 hippocampal slice cultures exposed to oxygen-glucose deprivation (OGD), and the neonatal rat exposed to HI. Both these processes were found to be nitric oxide (NO) dependent. Further analysis demonstrated that the NO-dependent increase in iron deposition was mediated through increased transferrin receptor expression and a decrease in ferritin expression. This was correlated with a reduction in aconitase activity. Both NO inhibition and iron scavenging, using deferoxamine administration, reduced hydroxyl radical levels and neuronal cell death. In conclusion, our results suggest that increased NO generation leads to neuronal cell death during neonatal HI, at least in part, by altering iron homeostasis and hydroxyl radical generation.

Original languageEnglish (US)
Pages (from-to)112-121
Number of pages10
JournalRedox Biology
Volume6
DOIs
StatePublished - Dec 1 2015

Fingerprint

Metabolism
Hydroxyl Radical
Brain
Nitric Oxide
Ischemia
Iron
Wounds and Injuries
Cell death
Brain Injuries
Cell Death
Aconitate Hydratase
Transferrin Receptors
Deferoxamine
Scavenging
Ferritins
Hydrogen Peroxide
Free Radicals
Rats
Homeostasis
Hypoxia

Keywords

  • Hydroxyl radical
  • Hypoxia-ischemia
  • Iron
  • Neonatal brain
  • Neuronal cell death
  • Nitric oxide

ASJC Scopus subject areas

  • Biochemistry
  • Organic Chemistry

Cite this

Nitric oxide induces hypoxia ischemic injury in the neonatal brain via the disruption of neuronal iron metabolism. / Lu, Qing; Harris, Valerie A.; Rafikov, Ruslan; Sun, Xutong; Kumar, Sanjiv; Black, Stephen Matthew.

In: Redox Biology, Vol. 6, 01.12.2015, p. 112-121.

Research output: Contribution to journalArticle

Lu, Qing ; Harris, Valerie A. ; Rafikov, Ruslan ; Sun, Xutong ; Kumar, Sanjiv ; Black, Stephen Matthew. / Nitric oxide induces hypoxia ischemic injury in the neonatal brain via the disruption of neuronal iron metabolism. In: Redox Biology. 2015 ; Vol. 6. pp. 112-121.
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