Takahashi Shinichi
Department of Neurology, Keio University School of Medicine.
Rinsho Shinkeigaku. 2011 Nov;51(11):1032-5. doi: 10.5692/clinicalneurol.51.1032.
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 Keap1/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.
神经细胞中线粒体产生的活性氧（ROS）在中风的病理生理学中起重要作用。已知高血糖也会增强ROS的产生，导致氧化应激。我们报道，急性和慢性高糖环境均会增强星形胶质细胞中的磷酸戊糖途径（PPP），减少ROS的产生，从而发挥神经保护作用。特别是，慢性高血糖通过Keap1/Nrf2系统引发PPP激活，该系统由内质网（ER）应激通过己糖胺生物合成途径通量增加诱导产生。我们研究了有无糖剥夺情况下缺氧对培养的神经元和星形胶质细胞中PPP的影响。无糖剥夺的缺氧12或24小时可诱导星形胶质细胞中PPP激活（分别为126%和177%），但对神经元无此作用。缺氧诱导的PPP激活伴随着Nrf2易位至细胞核，但不伴随着ER中Bip的表达。在有无糖剥夺的情况下缺氧12小时后再给氧并补充葡萄糖，可显著增强星形胶质细胞中的PPP（分别为231%和178%）。缺氧诱导星形胶质细胞中PPP激活，发挥神经保护作用。虽然Keap1/Nrf2系统似乎参与其中，但不一定需要ER应激。
