【摘 要】
：
The ubiquitin-proteasome system (UPS) is the major degradation pathway for intracellular proteins.The impairment and/or overload of the ubiquitin-proteasome
【机 构】
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Institute of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Acndemy of Sciences,
【出 处】
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中国神经科学学会第四次会员代表大会暨第七届全国学术会议(The 7th Biennial Meeting and the
论文部分内容阅读
The ubiquitin-proteasome system (UPS) is the major degradation pathway for intracellular proteins.The impairment and/or overload of the ubiquitin-proteasome pathway are likely to be major contributors to neurodegeneration.Deposition of ubiquitinated protein aggregates is a common hallmark of neurodegeneration in both acute conditions,such as stroke,and chronic neurodegenerative conditions,such as Parkinsons disease,but the underlying mechanisms are poorly understood.Here we report that ubiquitin conjugation and protein aggregation increased in the CA 1 region of rat hippocampus after transient forebrain ischemia.Scavenging endogenous Zn2+ with CaEDTA reduced ischemia-induced ubiquitin conjugation,protein aggregation.Furthermore,exposure to zinc chloride increased ubiquitin conjugation and inhibited the proteasome enzymic activity in cultured hippocampal neurons in a concentration-and time-dependent manner.Thus,Zn2+ mediated ischemia-induced ubiquitin conjugation and protein aggregation in the hippocampus.We predict that alterations in Zn2+ homeostasis will impair protein quality control/degradation pathway and may contribute to the pathogeneses of diverse human neurological diseases.
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