Department of Neurobiology, University of Pittsburgh School of Medicine, 3500 Terrace St., Pittsburgh, PA 15261, USA.
Antioxid Redox Signal. 2011 Oct 15;15(8):2249-63. doi: 10.1089/ars.2010.3607. Epub 2011 Mar 31.
Zn(2+) has emerged as a major regulator of neuronal physiology, as well as an important signaling agent in neural injury. The intracellular concentration of this metal is tightly regulated through the actions of Zn(2+) transporters and the thiol-rich metal binding protein metallothionein, closely linking the redox status of the cell to cellular availability of Zn(2+). Accordingly, oxidative and nitrosative stress during ischemic injury leads to an accumulation of neuronal free Zn(2+) and the activation of several downstream cell death processes. While this Zn(2+) rise is an established signaling event in neuronal cell death, recent evidence suggests that a transient, sublethal accumulation of free Zn(2+) can also play a critical role in neuroprotective pathways activated during ischemic preconditioning. Thus, redox-sensitive proteins, like metallothioneins, may play a critical role in determining neuronal cell fate by regulating the localization and concentration of intracellular free Zn(2+).
锌（2+）已成为神经元生理学的主要调节剂，也是神经损伤中重要的信号剂。这种金属的细胞内浓度通过锌（2+）转运体和富含巯基的金属结合蛋白金属硫蛋白的作用来严格调节，将细胞的氧化还原状态与细胞中锌（2+）的可用性紧密联系起来。因此，在缺血性损伤过程中的氧化和硝化应激导致神经元游离锌（2+）的积累和几种下游细胞死亡过程的激活。虽然这种锌（2+）上升是神经元细胞死亡中的一个既定信号事件，但最近的证据表明，游离锌（2+）的短暂、亚致死积累也可以在缺血预处理激活的神经保护途径中发挥关键作用。因此，像金属硫蛋白这样的氧化还原敏感蛋白，可能通过调节细胞内游离锌（2+）的定位和浓度，在决定神经元细胞命运方面发挥关键作用。
