Calcium-dependent proteasome activation is required for axonal neurofilament degradation  

作　　者：Joo Youn Park So Young Jang Yoon Kyung Shin Duk Joon Suh Hwan Tae Park 

机构地区：[1]Department of Physiology, Mitochondria Hub Regulation Center, College of Medicine, Dong-A University

出　　处：《Neural Regeneration Research》2013年第36期3401-3409,共9页中国神经再生研究（英文版）

基　　金：supported by research funds from Dong-A University,South Korea

摘　　要：Even though many studies have identified roles of proteasomes in axonal degeneration, the mo- lecular mechanisms by which axonal injury regulates proteasome activity are still unclear. In the present study, we found evidence indicating that extracellular calcium influx is an upstream regulator of proteasome activity during axonal degeneration in injured peripheral nerves. In degenerating axons, the increase in proteasome activity and the degradation of ubiquitinated proteins were sig- nificantly suppressed by extracellular calcium chelation. In addition, electron microscopic findings revealed selective inhibition of neurofilament degradation, but not microtubule depolymerization or mitochondrial swelling, by the inhibition of calpain and proteasomes. Taken together, our findings suggest that calcium increase and subsequent proteasome activation are an essential initiator of neurofilament degradation in Wallerian degeneration.Even though many studies have identified roles of proteasomes in axonal degeneration, the mo- lecular mechanisms by which axonal injury regulates proteasome activity are still unclear. In the present study, we found evidence indicating that extracellular calcium influx is an upstream regulator of proteasome activity during axonal degeneration in injured peripheral nerves. In degenerating axons, the increase in proteasome activity and the degradation of ubiquitinated proteins were sig- nificantly suppressed by extracellular calcium chelation. In addition, electron microscopic findings revealed selective inhibition of neurofilament degradation, but not microtubule depolymerization or mitochondrial swelling, by the inhibition of calpain and proteasomes. Taken together, our findings suggest that calcium increase and subsequent proteasome activation are an essential initiator of neurofilament degradation in Wallerian degeneration.

关 键 词：neural regeneration peripheral nerve injury neurofilament degradation sciatic nerve CALCIUM calpain mitochondria microtubule depolymerization axon axon degeneration neuroregeneration 

分 类 号：R341[医药卫生—基础医学]