Astroglial pentose phosphate pathway rates in response to high-glucose environments

Shinichi Takahashi, Yoshikane Izawa, Norihiro Suzuki

研究成果: Article

47 引用 (Scopus)

抜粋

ROS (reactive oxygen species) play an essential role in the pathophysiology of diabetes, stroke and neurodegenerative disorders. Hyperglycaemia associated with diabetes enhances ROS production and causes oxidative stress in vascular endothelial cells, but adverse effects of either acute or chronic high-glucose environments on brain arenchymal cells remain unclear. The PPP (pentose phosphate pathway) and GSH participate in a major defence mechanism against ROS in brain, and we explored the role and regulation of the astroglial PPP in response to acute and chronic high-glucose environments. PPP activity was measured in cultured neurons and astroglia by determining the difference in rate of 14CO 2 production from [1- 14C]glucose and [6- 14C]glucose. ROS production, mainly H 2O 2, and GSH were also assessed. Acutely elevated glucose concentrations in the culture media increased PPP activity and GSH level in astroglia, decreasing ROS production. Chronically elevated glucose environments also induced PPP activation. Immunohistochemical analyses revealed that chronic high-glucose environments induced ER (endoplasmic reticulum) stress (presumably through increased hexosamine biosynthetic pathway flux). Nuclear translocation of Nrf2 (nuclear factor-erythroid 2 p45 subunit-related factor 2), which regulates G6PDH (glyceraldehyde-6-phosphate dehydrogenase) by enhancing transcription, was also observed in association with BiP (immunoglobulin heavy-chain-binding protein) expression. Acute and chronic high-glucose environments activated the PPP in astroglia, preventing ROS elevation. Therefore a rapid decrease in glucose level seems to enhance ROS toxicity, perhaps contributing to neural damage when insulin levels given to diabetic patients are not properly calibrated and plasma glucose levels are not adequately maintained. These findings may also explain the lack of evidence for clinical benefits from strict glycaemic control during the acute phase of stroke.

元の言語English
ページ(範囲)71-88
ページ数18
ジャーナルASN neuro
4
発行部数2
DOI
出版物ステータスPublished - 2012 4 2

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology

フィンガープリント Astroglial pentose phosphate pathway rates in response to high-glucose environments' の研究トピックを掘り下げます。これらはともに一意のフィンガープリントを構成します。

  • これを引用