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The anti-inflammatory role of extranuclear apurinic/apyrimidinic endonuclease 1/redox effector factor-1 in reactive astrocytes

Overview of attention for article published in Molecular Brain, December 2016
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Title
The anti-inflammatory role of extranuclear apurinic/apyrimidinic endonuclease 1/redox effector factor-1 in reactive astrocytes
Published in
Molecular Brain, December 2016
DOI 10.1186/s13041-016-0280-9
Pubmed ID
Authors

Hyunjung Baek, Chae Seong Lim, Hee Sun Byun, Hyun Sil Cho, Yu Ran Lee, Yong Sup Shin, Hyun-Woo Kim, Byeong Hwa Jeon, Dong Woon Kim, Jinpyo Hong, Gang Min Hur, Jin Bong Park

Abstract

Apurinic/apyrimidinic endonuclease 1 (APE1), a ubiquitous multipurpose protein, is also known as redox effector factor-1 (Ref-1). It is involved in DNA repair and redox signaling and, in turn, oxidative stress-induced neurodegeneration. Although previous studies have demonstrated that APE1/Ref-1 functions as a negative regulator of inflammatory response via several mechanisms in neuronal cells, little is known about the roles of APE1/Ref-1 in glial cells. In this study, we found that cytoplasmic APE1/Ref-1 expression was upregulated in reactive astrocytes of the kainic acid- or lipopolysaccharide (LPS)-injected hippocampus. Analysis of the inflammatory response induced by extranuclear APE1/Ref-1 (ΔNLS-Ref-1) in cultured primary astrocytes revealed that it markedly suppressed inducible nitric oxide synthase (iNOS) expression and tumor necrosis factor-α (TNF-α) secretion induced by LPS to a similar extent as did wild type APE1/Ref-1 (WT-Ref-1), supporting the concept an anti-inflammatory role of extranuclear APE1/Ref-1 in astrocytes. Additionally, overexpression of WT- and ΔNLS-Ref-1 suppressed the transcriptional activity of nuclear factor-κB (NF-κB), although it effectively enhanced activator protein 1 (AP-1) activity. The blunting effect of APE1/Ref-1 on LPS-induced NF-κB activation was not mediated by IκB kinase (IKK) activity. Instead, APE1/Ref-1 inhibited p300-mediated acetylation of p65 by suppressing intracellular reactive oxygen species (ROS) levels following LPS treatment. Taken together, our results showed that altered expression and/or subcellular distribution of APE1/Ref-1 in activated astrocytes regulated the neuroinflammatory response to excitotoxin and endotoxin insults used in model of neurodegenerative brain diseases.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 33 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 33 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 6 18%
Student > Ph. D. Student 4 12%
Professor 4 12%
Student > Postgraduate 4 12%
Student > Master 3 9%
Other 7 21%
Unknown 5 15%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 9 27%
Agricultural and Biological Sciences 6 18%
Medicine and Dentistry 4 12%
Neuroscience 3 9%
Veterinary Science and Veterinary Medicine 1 3%
Other 3 9%
Unknown 7 21%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 28 December 2016.
All research outputs
#18,504,575
of 22,925,760 outputs
Outputs from Molecular Brain
#867
of 1,114 outputs
Outputs of similar age
#310,044
of 421,075 outputs
Outputs of similar age from Molecular Brain
#8
of 12 outputs
Altmetric has tracked 22,925,760 research outputs across all sources so far. This one is in the 11th percentile – i.e., 11% of other outputs scored the same or lower than it.
So far Altmetric has tracked 1,114 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 7.0. This one is in the 1st percentile – i.e., 1% of its peers scored the same or lower than it.
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We're also able to compare this research output to 12 others from the same source and published within six weeks on either side of this one. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.