PMID- 25633295
OWN - NLM
STAT- MEDLINE
DCOM- 20150911
LR  - 20220318
IS  - 2041-4889 (Electronic)
VI  - 6
IP  - 1
DP  - 2015 Jan 29
TI  - Inhibition of immunoproteasome reduces infarction volume and attenuates 
      inflammatory reaction in a rat model of ischemic stroke.
PG  - e1626
LID - 10.1038/cddis.2014.586 [doi]
AB  - The detailed knowledge about the contribution of immunoproteasome to the 
      neuroinflammation in ischemic stroke is still not available. The immunoreactivity 
      of low molecular mass peptide 2 (LMP2) and low molecular mass peptide 7 (LMP7) 
      was evident in the ipsilateral ischemic cerebral cortex and striatum following 
      transient middle cerebral artery occlusion (MCAO). Both LMP2 and LMP7 increased 
      as early as 4 h after the MCAO, further increased at 24 h, peaked at 72 h and 
      decreased 7 days later. LMP2 and LMP7 were mainly present in astrocytes and 
      microglia/macrophage cells, respectively. LMP2 knockdown by shRNA (short hairpin 
      RNA) markedly reduced the levels of LMP2 and LMP7 protein and caused 75.5 and 
      78.6% decrease in the caspase-like (C-L) and chymotrypsin-like (CT-L) activities, 
      respectively. Compared with cont-shRNA group (39.7%, infarction volumes/total 
      ipsilateral hemisphere), the infarction volumes were reduced to 22.5% in 
      LMP2-shRNA group. Additionally, LMP2 knockdown significantly reduced activated 
      astrocytes and microglia, the expression nuclear factor kappa B (NF-kappaB) p65, 
      tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) and caused less 
      accumulation of ischemia-induced protein ubiquitination compared with MG132. 
      These findings demonstrate that inhibition of LMP2 significantly attenuates 
      inflammatory reaction and offers neuroprotection against focal cerebral ischemia 
      in rats, suggesting that selective immunoproteasome inhibitors may be a promising 
      strategy for stroke treatment.
FAU - Chen, X
AU  - Chen X
AD  - 1] Department of Neurology, National Key Clinical Department and Key Discipline 
      of Neurology, Guangdong Key Laboratory for Diagnosis and Treatment of Major 
      Neurological Diseases, The First Affiliated Hospital, Sun Yat-Sen University, 
      Guangzhou 510080, PR China [2] Department of Neurology, Fujian Provincial 
      Hospital, Fujian Medical University Shengli Clinical College, Fuzhou 350001, PR 
      China.
FAU - Zhang, X
AU  - Zhang X
AD  - Department of Neurology, Fujian Provincial Hospital, Fujian Medical University 
      Shengli Clinical College, Fuzhou 350001, PR China.
FAU - Wang, Y
AU  - Wang Y
AD  - Department of Neurology, Fujian Provincial Hospital, Fujian Medical University 
      Shengli Clinical College, Fuzhou 350001, PR China.
FAU - Lei, H
AU  - Lei H
AD  - Department of Neurology, Fujian Provincial Hospital, Fujian Medical University 
      Shengli Clinical College, Fuzhou 350001, PR China.
FAU - Su, H
AU  - Su H
AD  - Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese 
      Medical Sciences, University of Macau, Macao, PR China.
FAU - Zeng, J
AU  - Zeng J
AD  - Department of Neurology, National Key Clinical Department and Key Discipline of 
      Neurology, Guangdong Key Laboratory for Diagnosis and Treatment of Major 
      Neurological Diseases, The First Affiliated Hospital, Sun Yat-Sen University, 
      Guangzhou 510080, PR China.
FAU - Pei, Z
AU  - Pei Z
AD  - Department of Neurology, National Key Clinical Department and Key Discipline of 
      Neurology, Guangdong Key Laboratory for Diagnosis and Treatment of Major 
      Neurological Diseases, The First Affiliated Hospital, Sun Yat-Sen University, 
      Guangzhou 510080, PR China.
FAU - Huang, R
AU  - Huang R
AD  - Department of Neurology, National Key Clinical Department and Key Discipline of 
      Neurology, Guangdong Key Laboratory for Diagnosis and Treatment of Major 
      Neurological Diseases, The First Affiliated Hospital, Sun Yat-Sen University, 
      Guangzhou 510080, PR China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150129
PL  - England
TA  - Cell Death Dis
JT  - Cell death & disease
JID - 101524092
RN  - 0 (Interleukin-1beta)
RN  - 0 (Leupeptins)
RN  - 0 (NF-kappa B)
RN  - 0 (Proteasome Inhibitors)
RN  - 0 (Protein Subunits)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (Ubiquitinated Proteins)
RN  - 144416-78-4 (LMP-2 protein)
RN  - EC 3.4.22.- (Cysteine Endopeptidases)
RN  - EC 3.4.25.1 (LMP7 protein)
RN  - EC 3.4.25.1 (Proteasome Endopeptidase Complex)
RN  - RF1P63GW3K (benzyloxycarbonylleucyl-leucyl-leucine aldehyde)
SB  - IM
MH  - Animals
MH  - Astrocytes/drug effects/metabolism
MH  - Cerebral Infarction/*complications/metabolism/*pathology
MH  - Cysteine Endopeptidases/metabolism
MH  - Disease Models, Animal
MH  - Gene Knockdown Techniques
MH  - Infarction, Middle Cerebral Artery/complications/metabolism/pathology
MH  - Inflammation/*pathology
MH  - Interleukin-1beta/metabolism
MH  - Leupeptins/pharmacology
MH  - Male
MH  - Microglia/drug effects/metabolism
MH  - NF-kappa B/metabolism
MH  - Proteasome Endopeptidase Complex/*immunology/metabolism
MH  - Proteasome Inhibitors/*pharmacology
MH  - Protein Subunits/metabolism
MH  - Protein Transport/drug effects
MH  - RNA, Small Interfering/metabolism
MH  - Rats, Sprague-Dawley
MH  - Stroke/*complications/*pathology
MH  - Tumor Necrosis Factor-alpha/metabolism
MH  - Ubiquitinated Proteins/metabolism
PMC - PMC4669779
EDAT- 2015/01/31 06:00
MHDA- 2015/09/12 06:00
PMCR- 2015/01/01
CRDT- 2015/01/31 06:00
PHST- 2014/08/31 00:00 [received]
PHST- 2014/11/19 00:00 [revised]
PHST- 2014/12/15 00:00 [accepted]
PHST- 2015/01/31 06:00 [entrez]
PHST- 2015/01/31 06:00 [pubmed]
PHST- 2015/09/12 06:00 [medline]
PHST- 2015/01/01 00:00 [pmc-release]
AID - cddis2014586 [pii]
AID - 10.1038/cddis.2014.586 [doi]
PST - epublish
SO  - Cell Death Dis. 2015 Jan 29;6(1):e1626. doi: 10.1038/cddis.2014.586.