Astroglial protective mechanisms against ROS under brain ischemia

Shinichi Takahashi

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Reactive oxygen species (ROS) derived from mitochondria in neural cells play an essential role in the pathophysiology of stroke. Hyperglycemia is also known to enhance ROS production, resulting in oxidative stress. We reported that both acute and chronic high glucose environments enhance the pentose phosphate pathway (PPP) in astroglia, reducing ROS production and thereby providing a neuroprotective role. In particular, chronic hyperglycemia elicits PPP activation through the Keapl/Nrf2 system, which is induced by endoplasmic (ER) stress via an increase in hexosamine biosynthetic pathway flux. We examined the effects of hypoxia with or without glucoprivation on PPP in cultured neurons and astroglia Hypoxia without glucoprivation for 12 or 24 hours induced PPP activation in astroglia (126% and 177%, respectively) but not in neurons. PPP activation by hypoxia was accompanied by Nrf2 translocation to the nucleus but not by Bip expression in the ER. Re-oxygenation supplemented with glucose after 12 hours of hypoxia with or without glucoprivation markedly enhanced PPP in astroglia (231% and 178%, respectively). Hypoxia induced PPP activation in astroglia exerting a neuroprotective role. While the Keap1/Nrf2 system seems to be involved, ER stress is not necessarily required.

Original languageEnglish
Pages (from-to)1032-1035
Number of pages4
JournalClinical Neurology
Volume51
Issue number11
DOIs
Publication statusPublished - 2011

Fingerprint

Pentose Phosphate Pathway
Brain Ischemia
Reactive Oxygen Species
Astrocytes
Hyperglycemia
Hexosamines
Neurons
Glucose
Biosynthetic Pathways
Mitochondria
Oxidative Stress
Stroke
Hypoxia

Keywords

  • Astroglia
  • Cerebral infarction
  • Keap1/Nrf2 system
  • Pentose-phosphate pathway
  • Reactive oxygen species

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Astroglial protective mechanisms against ROS under brain ischemia. / Takahashi, Shinichi.

In: Clinical Neurology, Vol. 51, No. 11, 2011, p. 1032-1035.

Research output: Contribution to journalArticle

Takahashi, Shinichi. / Astroglial protective mechanisms against ROS under brain ischemia. In: Clinical Neurology. 2011 ; Vol. 51, No. 11. pp. 1032-1035.
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