Ubiquilin-1 protects cells from oxidative stress and ischemic stroke caused tissue injury in mice

Yanying Liu, Lanhai Lü, Casey L. Hettinger, Gaofeng Dong, Dong Zhang, Khosrow Rezvani, Xuejun Wang, Hongmin Wang

Research output: Contribution to journalArticle

32 Citations (Scopus)

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 theWTlittermates 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.

Original languageEnglish (US)
Pages (from-to)2813-2821
Number of pages9
JournalJournal of Neuroscience
Volume34
Issue number8
DOIs
StatePublished - Feb 25 2014

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Oxidative Stress
Stroke
Transgenic Mice
Wounds and Injuries
Proteasome Endopeptidase Complex
Ubiquitins
Ubiquitinated Proteins
Proteins
Ubiquitin
Knockout Mice
Proteolysis
Reperfusion
Ischemia
Therapeutics

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Ubiquilin-1 protects cells from oxidative stress and ischemic stroke caused tissue injury in mice. / Liu, Yanying; Lü, Lanhai; Hettinger, Casey L.; Dong, Gaofeng; Zhang, Dong; Rezvani, Khosrow; Wang, Xuejun; Wang, Hongmin.

In: Journal of Neuroscience, Vol. 34, No. 8, 25.02.2014, p. 2813-2821.

Research output: Contribution to journalArticle

Liu, Yanying ; Lü, Lanhai ; Hettinger, Casey L. ; Dong, Gaofeng ; Zhang, Dong ; Rezvani, Khosrow ; Wang, Xuejun ; Wang, Hongmin. / Ubiquilin-1 protects cells from oxidative stress and ischemic stroke caused tissue injury in mice. In: Journal of Neuroscience. 2014 ; Vol. 34, No. 8. pp. 2813-2821.
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