title: Ubiquilin-1 protects cells from oxidative stress and ischemic stroke caused tissue injury in mice.
abstract: 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.
authors.affiliation: Division of Basic Biomedical Sciences, Sanford School of Medicine, University of South Dakota, Vermillion, South Dakota 57069.
authors.forename: Yanying
authors.initials: Y
authors.lastname: Liu
authors.forename: Lanhai
authors.initials: L
authors.lastname: Lü
authors.forename: Casey L
authors.initials: CL
authors.lastname: Hettinger
authors.forename: Gaofeng
authors.initials: G
authors.lastname: Dong
authors.forename: Dong
authors.initials: D
authors.lastname: Zhang
authors.forename: Khosrow
authors.initials: K
authors.lastname: Rezvani
authors.forename: Xuejun
authors.initials: X
authors.lastname: Wang
authors.forename: Hongmin
authors.initials: H
authors.lastname: Wang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport / Q000502:physiology*; D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D000071183:Autophagy-Related Proteins; D015153:Blotting, Western; D002545:Brain Ischemia / Q000235:genetics* / Q000473:pathology; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D005452:Fluoresceins; D005456:Fluorescent Dyes; D002546:Ischemic Attack, Transient / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D018384:Oxidative Stress / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D004856:Postural Balance / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism; D015427:Reperfusion Injury / Q000473:pathology; D020521:Stroke / Q000235:genetics* / Q000473:pathology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D000071183:Autophagy-Related Proteins; D018076:DNA, Complementary; D005452:Fluoresceins; D005456:Fluorescent Dyes; D017382:Reactive Oxygen Species; C538987:UBQLN1 protein, mouse; C435731:fluoro jade