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Inhibition of cysteine cathepsin B and L activation in astrocytes contributes to neuroprotection against cerebral ischemia via blocking the tBid‐mitochondrial apoptotic signaling pathway

Overview of attention for article published in Glia, February 2014
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Title
Inhibition of cysteine cathepsin B and L activation in astrocytes contributes to neuroprotection against cerebral ischemia via blocking the tBid‐mitochondrial apoptotic signaling pathway
Published in
Glia, February 2014
DOI 10.1002/glia.22645
Pubmed ID
Authors

Min Xu, Lei Yang, Jia‐Guo Rong, Yong Ni, Wei‐Wei Gu, Yu Luo, Kazumi Ishidoh, Nobuhiko Katunuma, Zhong‐Sheng Li, Hui‐Ling Zhang

Abstract

The roles of cathepsins in the ischemic astrocytic injury remain unclear. Here, we test the hypothesis that activation of cathepsin B and L contributes to the ischemic astrocyte injury via the tBid-mitochondrial apoptotic signaling pathways. In the rat models of pMCAO, CA-074Me or Clik148, a selective inhibitor of cathepsin B or cathepsin L, reduced the infarct volume, improved the neurological deficits and increased the MAP2 and GFAP levels. In OGD-induced astrocyte injury, CA-074Me or Clik148 decreased the LDH leakage and increased the GFAP levels. In the ischemic cortex or OGD-induced astrocytes injury, Clik148 or CA-074Me reversed pMCAO or OGD-induced increase in active cathepsin L or cathepsin B at 3 h or 6 h, increase in tBid, reduction in mitochondrial cytochrome-c (Cyt-c) and increase in cytoplastic Cyt-c and active caspase-3 at 12-24 h of the late stage of pMCAO or OGD. CA-074Me or Clik148 also reduced cytosolic and mitochondrial tBid, increased mitochondrial Cyt-c and decreased cytoplastic Cyt-c and active caspase-3 at 6 h of the early stage of Bid activation. CA-074Me or Clik148 blocked the pMCAO-induced release of cathepsin B or L from the lysosomes into the cytoplasm and activation of caspase-3 in ischemic astrocytes at 12 h after ischemia. Concurrent inhibition of cathepsin B and cathepsin L provided better protection on the OGD-induced astrocytic apoptosis than obtained with separate use of each inhibitor. These results suggest that inhibition of the cysteine cathepsin B and cathepsin L activation in ischemic astrocytes contributes to neuroprotection via blocking the tBid-mitochondrial apoptotic signaling pathway.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 24 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 24 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 5 21%
Student > Bachelor 4 17%
Student > Doctoral Student 3 13%
Student > Master 3 13%
Researcher 2 8%
Other 2 8%
Unknown 5 21%
Readers by discipline Count As %
Neuroscience 5 21%
Biochemistry, Genetics and Molecular Biology 4 17%
Agricultural and Biological Sciences 2 8%
Chemistry 2 8%
Medicine and Dentistry 2 8%
Other 4 17%
Unknown 5 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 24 February 2014.
All research outputs
#19,995,718
of 24,571,708 outputs
Outputs from Glia
#1,942
of 2,354 outputs
Outputs of similar age
#168,630
of 228,735 outputs
Outputs of similar age from Glia
#24
of 41 outputs
Altmetric has tracked 24,571,708 research outputs across all sources so far. This one is in the 10th percentile – i.e., 10% of other outputs scored the same or lower than it.
So far Altmetric has tracked 2,354 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.9. This one is in the 7th percentile – i.e., 7% of its peers scored the same or lower than it.
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We're also able to compare this research output to 41 others from the same source and published within six weeks on either side of this one. This one is in the 4th percentile – i.e., 4% of its contemporaries scored the same or lower than it.