Autophagy in neonatal hypoxia ischemic brain is associated with oxidative stress

Qing Lu, Valerie A. Harris, Sanjiv Kumar, Heidi M. Mansour, Stephen Matthew Black

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Autophagy is activated when the neonatal brain exposed to hypoxia ischemia (HI), but the mechanisms underlying its activation and its role in the neuronal cell death associated with HI is unclear. We have previously shown that reactive oxygen species (ROS) derived from nicotinamide adenine dinucleotide phosphate (NADPH) oxidase play an important role in HI-mediated neuronal cell death. Thus, the aim of this study was to determine if ROS is involved in the activation of autophagy in HI-mediated neonatal brain injury and to determine if this is a protective or deleterious pathway. Initial electron microscopy data demonstrated that autophagosome formation is elevated in P7 hippocampal slice cultures exposed to oxygen-glucose deprivation (OGD). This corresponded with increased levels of LC3II mRNA and protein. The autophagy inhibitor, 3-methyladenine (3-MA) effectively reduced LC3II levels and autophagosome formation in hippocampal slice cultures exposed to OGD. Neuronal cell death was significantly attenuated. Finally, we found that the pharmacologic inhibition of NADPH oxidase using apocynin or gp91ds-tat decreased autophagy in hippocampal slice cultures and the rat brain respectively. Thus, our results suggest that an activation of autophagy contributes to neonatal HI brain injury this is oxidative stress dependent.

Original languageEnglish (US)
Pages (from-to)516-523
Number of pages8
JournalRedox Biology
Volume6
DOIs
StatePublished - Dec 1 2015

Fingerprint

Brain Hypoxia
Oxidative stress
Autophagy
Brain
Oxidative Stress
Cell death
Ischemia
Chemical activation
NADP
Cell Death
Reactive Oxygen Species
Oxidoreductases
Brain Injuries
Oxygen
Glucose
Cell culture
Electron microscopy
Rats
Hippocampus
Electron Microscopy

Keywords

  • Autophagy
  • Hypoxia-ischemia
  • NADPH oxidase
  • Neonatal brain
  • Neuronal cell death

ASJC Scopus subject areas

  • Biochemistry
  • Organic Chemistry

Cite this

Autophagy in neonatal hypoxia ischemic brain is associated with oxidative stress. / Lu, Qing; Harris, Valerie A.; Kumar, Sanjiv; Mansour, Heidi M.; Black, Stephen Matthew.

In: Redox Biology, Vol. 6, 01.12.2015, p. 516-523.

Research output: Contribution to journalArticle

Lu, Qing ; Harris, Valerie A. ; Kumar, Sanjiv ; Mansour, Heidi M. ; Black, Stephen Matthew. / Autophagy in neonatal hypoxia ischemic brain is associated with oxidative stress. In: Redox Biology. 2015 ; Vol. 6. pp. 516-523.
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