کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2200775 1099971 2012 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Knockdown of glucose-6-phosphate dehydrogenase (G6PD) following cerebral ischemic reperfusion: The pros and cons
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی بیولوژی سلول
پیش نمایش صفحه اول مقاله
Knockdown of glucose-6-phosphate dehydrogenase (G6PD) following cerebral ischemic reperfusion: The pros and cons
چکیده انگلیسی

NADPH derived from glucose-6-phosphate dehydrogenase (G6PD), the rate-limiting enzyme of the pentose phosphate pathway, has been implicated not only to promote reduced glutathione (GSH) but also enhance oxidative stress in specific cellular conditions. In this study, the effects of G6PD antisense oligodeoxynucleotides (AS-ODNs) was examined on the CA1 pyramidal neurons following transient cerebral ischemia. Specifically knockdown of G6PD protein expression in hippocampus CA1 subregion at early reperfusion period (1–24 h) with a strategy to pre-treated G6PD AS-ODNs significantly reduced G6PD activity and NADPH level, an effect correlated with attenuation of NADPH oxidase activation and superoxide anion production. Concomitantly, pre-treatment of G6PD AS-ODNs markedly reduced oxidative DNA damage and the delayed neuronal cell death in rat hippocampal CA1 region induced by global cerebral ischemia. By contrast, knockdown of G6PD protein at late reperfusion period (48–96 h) increased oxidative DNA damage and exacerbated the ischemia-induced neuronal cell death in hippocampal CA1 region, an effect associated with reduced NADPH level and GSH/GSSG ratio. These findings indicate that G6PD not only plays a role in oxidative neuronal damage but also a neuroprotective role during different ischemic reperfusion period. Therefore, G6PD mediated oxidative response and redox regulation in the hippocampal CA1 act as the two sides of the same coin and may represent two potential applications of G6PD during different stage of cerebral ischemic reperfusion.


► G6PD knockdown at early ischemic reperfusion reduced NADPH and superoxide levels.
► G6PD knockdown at early ischemic reperfusion reduced oxidative neuronal damage.
► G6PD knockdown at late ischemic reperfusion reduced NADPH level and GSH/GSSG ratio.
► G6PD knockdown at late ischemic reperfusion increased oxidative neuronal damage.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neurochemistry International - Volume 61, Issue 2, July 2012, Pages 146–155
نویسندگان
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