RT Journal Article
SR Electronic
T1 Ubiquilin-1 Protects Cells from Oxidative Stress and Ischemic Stroke Caused Tissue Injury in Mice
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 2813
OP 2821
DO 10.1523/JNEUROSCI.3541-13.2014
VO 34
IS 8
A1 Yanying Liu
A1 Lanhai Lü
A1 Casey L. Hettinger
A1 Gaofeng Dong
A1 Dong Zhang
A1 Khosrow Rezvani
A1 Xuejun Wang
A1 Hongmin Wang
YR 2014
UL http://www.jneurosci.org/content/34/8/2813.abstract
AB Ubiquilin-1 (Ubqln1 or Ubqln), a ubiquitin-like protein, mediates degradation of misfolded proteins and has been implicated in a number of pathological and physiological conditions. To better understand its function in vivo, we recently generated transgenic (Tg) mice that globally overexpress mouse Ubqln in a variety of tissues and ubqln conditional knock-out mice. The Tg mice were viable and did not show any developmental or behavioral abnormalities compared with their wild-type (WT) littermates. When subjected to oxidative stress or ischemia/reperfusion, however, ubqln Tg mice but not the WT littermates showed increased tolerance to these insults. Following ischemic stroke, ubqln Tg mice recovered motor function more rapidly than did the WT mice. In contrast, KO of ubqln exacerbated neuronal damage after stroke. In addition, KO of ubqln also caused accumulation of ubiquitinated proteins. When ubqln KO mice were crossed with a ubiquitin-proteasome system function reporter mouse, the accumulation of a proteasome surrogate substrate was observed. These results suggest that Ubqln protects mice from oxidative stress and ischemic stroke-caused neuronal injury through facilitating removal of damaged proteins. Thus, enhanced removal of unwanted proteins is a potential therapeutic strategy for treating stroke-caused neuronal injury.