Bolaños Juan P, Almeida Angeles
Departamento de Bioquímica y Biología Molecular, Universidad de Salamanca/Instituto de Neurociencias de Castilla y León, Centro Nacional de Investigaciones Cardiovasculares, Campus Miguel de Unamuno, Salamanca, Spain.
Antioxid Redox Signal. 2006 May-Jun;8(5-6):955-65. doi: 10.1089/ars.2006.8.955.
Activated astroglial cells produce large amounts of nitric oxide (NO) which, through the binding to soluble guanylyl cyclase, rapidly increases cyclic GMP concentrations. In addition, through the binding with the a-a (3) binuclear center of cytochrome c oxidase, NO rapidly decreases the affinity of this complex for O(2), hence reversibly inhibiting the mitochondrial electron flux and ATP synthesis. Despite promoting a profound degree of mitochondrial inhibition, astrocytes show remarkable resistance to NO and peroxynitrite, whereas neurons are highly vulnerable. Recent evidence suggests that the inhibition of mitochondrial respiration by these nitrogen-derived reactive species leads to the modulation of key regulatory steps of glucose metabolism. Thus, upregulation of glucose uptake, the stimulation of glycolysis and the activation of pentose-phosphate pathway appear to be important sites of action. The stimulation of these glucose-metabolizing pathways by NO would represent a transient attempt by the glial cells to compensate for energy impairment and oxidative stress, and thus to emerge from an otherwise pathological outcome.
活化的星形胶质细胞会产生大量一氧化氮（NO），该物质通过与可溶性鸟苷酸环化酶结合，迅速提高环磷酸鸟苷（cGMP）的浓度。此外，NO通过与细胞色素c氧化酶的α-α（3）双核中心结合，迅速降低该复合物对O₂的亲和力，从而可逆地抑制线粒体电子传递和ATP合成。尽管会导致深度的线粒体抑制，但星形胶质细胞对NO和过氧亚硝酸盐具有显著的抗性，而神经元则高度敏感。最近的证据表明，这些氮衍生的活性物质对线粒体呼吸的抑制作用会导致葡萄糖代谢关键调控步骤的调节。因此，葡萄糖摄取的上调、糖酵解的刺激以及磷酸戊糖途径的激活似乎是重要的作用位点。NO对这些葡萄糖代谢途径的刺激作用可能代表着胶质细胞为补偿能量损伤和氧化应激而进行的短暂尝试，从而避免出现病理结果。
