Wang, HD (reprint author), Nanjing Univ, Dept Neurosurg, Jinling Hosp, Sch Med, 305 E Zhongshan Rd, Nanjing 210002, Jiangsu, Peoples R China,email@example.com
There is increasing evidence showing that zinc plays a key role in inducing neuronal death during central nervous system injury. However, the underlying mechanisms are poorly understood. Here we assessed the effect of zinc on ubiquitin conjugation and subsequent neurodegeneration using cultured hippocampal cells. We report that cultured neurons are vulnerable to increased level of extracellular Zn2+. Zn2+-induced poly-ubiquitination in cultured neurons is in a concentration- and time-dependent manner. Furthermore our data demonstrated that Zn2+-induced ubiquitination requires p38 activation. These findings indicate that excessive zinc could impair the protein degradation pathway and may be a crucial factor mediating neuronal death following traumatic brain injury. Crown Copyright (C) 2012 Published by Elsevier B.V. All rights reserved.