Research ReportZinc as mediator of ubiquitin conjugation following traumatic brain injury

Previous studies have shown that pathological zinc accumulation and deposition of ubiquitinated protein aggregates are commonly detected in many acute neural injuries, such as trauma, epilepsy and ischemia. However, the underlying mechanisms are poorly understood. Here we assessed the effect of zinc on ubiquitin conjugation and subsequent neurodegeration following traumatic brain injury (TBI). First, we found that scavenging endogenous Zn2+ reduced trauma-induced ubiquitin conjugation and protected neurons from TBI insults in rat hippocampus. Second, we detected both zinc accumulation and increased ubiquitin conjugated protein following brain trauma in human cortical neurons. Our previous study has shown that zinc can induce ubiquitin conjugation in cultured hippocampal neurons. All these findings indicate that alterations in Zn2+ homeostasis may impair the protein degradation pathway and ultimately cause neuronal injury following traumatic brain injury.

► Endogenous Zn2+ mediates TBI-induced ubiquitination in injured neurons. ► Human TBI could induce abnormal zinc accumulation in injured neurons. ► Increased protein ubiquitination was observed in neurons following the TBI in human.