Journal
REDOX BIOLOGY
Volume 6, Issue -, Pages 112-121Publisher
ELSEVIER
DOI: 10.1016/j.redox.2015.06.007
Keywords
Hypoxia-ischemia; Neuronal cell death; Iron; Hydroxyl radical; Nitric oxide; Neonatal brain
Categories
Funding
- National Institutes of Health [HL60190, HL67841, HL101902, HD039110]
- American Heart Association National Office [14SDG20480354]
Ask authors/readers for more resources
We have recently shown that increased hydrogen peroxide (H2O2) generation is involved in hypoxiaischemia (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. (C) 2015 The Authors. Published by Elsevier B.V.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available