Redox regulation of intracellular zinc: molecular signaling in the life and death of neurons.
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+).
Aras
Mandar A
MA
Department of Neurobiology, University of Pittsburgh School of Medicine, 3500 Terrace St., Pittsburgh, PA 15261, USA. mandararas@gmail.com
Aizenman
Elias
E
D000818:Animals; D006801:Humans; D008668:Metallothionein / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D010084:Oxidation-Reduction; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D015032:Zinc / Q000378:metabolism*
D008668:Metallothionein; D015032:Zinc