Premium
Zn 2+ mediates ischemia‐induced impairment of the ubiquitin‐proteasome system in the rat hippocampus
Author(s) -
Chen Min,
Chen Qian,
Cheng XueWen,
Lu TingJia,
Liu HanXing,
Jia JieMin,
Zhang Chi,
Xu Li,
Xiong ZhiQi
Publication year - 2009
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2009.06401.x
Subject(s) - ubiquitin , neurodegeneration , proteasome , hippocampal formation , hippocampus , ischemia , endogeny , microbiology and biotechnology , chemistry , homeostasis , biology , medicine , endocrinology , biochemistry , disease , gene
Deposition of ubiquitinated protein aggregates is a hallmark of neurodegeneration in both acute neural injuries, such as stroke, and chronic conditions, such as Parkinson’s disease, but the underlying mechanisms are poorly understood. In the present study, we examined the role of Zn 2+ in ischemia‐induced impairment of the ubiquitin‐proteasome system in the CA1 region of rat hippocampus after transient global ischemia. We found that scavenging endogenous Zn 2+ reduced ischemia‐induced ubiquitin conjugation and free ubiquitin depletion. Furthermore, exposure to zinc chloride increased ubiquitination and inhibited proteasomal enzyme activity in cultured hippocampal neurons in a concentration‐ and time‐dependent manner. Further studies of the underlying mechanisms showed that Zn 2+ ‐induced ubiquitination required p38 activation. These findings indicate that alterations in Zn 2+ homeostasis impair the protein degradation pathway.