Quantitative mass spectrometric analysis of the mouse cerebral cortex after ischemic stroke

Ischemic strokes result in the death of brain tissue and a wave of downstream effects, often leading to lifelong disabilities or death. However, the underlying mechanisms of ischemic damage and repair systems remain largely unknown. In order to better understand these mechanisms, TMT-isobaric mass t...

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Bibliographic Details
Published in:PloS one 2020-04, Vol.15 (4), p.e0231978
Main Authors: Agarwal, Ank, Park, Seongje, Ha, Shinwon, Kwon, Ji-Sun, Khan, Mohammed Repon, Kang, Bong Gu, Dawson, Ted M, Dawson, Valina L, Andrabi, Shaida A, Kang, Sung-Ung
Format: Article
Language:English
Subjects:
Adenosine diphosphate
Biology and Life Sciences
Brain
Brain research
Cell death
Cerebral blood flow
Cerebral cortex
Disabilities
Engineering
Functional groups
Gene expression
Ischemia
Labeling
Marking
Mass spectrometry
Mass spectroscopy
Medical research
Medicine
Medicine and Health Sciences
Membrane proteins
Membranes
Molecular modelling
Mortality
Neurology
Neurosciences
Occlusion
Outer membrane proteins
Peptides
Protein expression
Proteins
Reperfusion
Ribose
Scientific imaging
Stem cells
Stroke
Tagging
Veins & arteries
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Summary:Ischemic strokes result in the death of brain tissue and a wave of downstream effects, often leading to lifelong disabilities or death. However, the underlying mechanisms of ischemic damage and repair systems remain largely unknown. In order to better understand these mechanisms, TMT-isobaric mass tagging and mass spectrometry were conducted on brain cortex extracts from mice subjected to one hour of middle cerebral artery occlusion (MCAO) and after one hour of reperfusion. In total, 2,690 proteins were identified and quantified, out of which 65% of the top 5% of up- and down-regulated proteins were found to be significant (p < 0.05). Network-based gene ontology analysis was then utilized to cluster all identified proteins by protein functional groups and cellular roles. Although three different cellular functions were identified-organelle outer membrane proteins, cytosolic ribosome proteins, and spliceosome complex proteins-several functional domains were found to be common. Of these, organelle outer membrane proteins were downregulated whereas cytosolic ribosome and spliceosome complex proteins were upregulated, indicating that major molecular events post-stroke were translation-associated and subsequent signaling pathways (e.g., poly (ADP-ribose) (PAR) dependent cell death). By approaching stroke analyses via TMT-isobaric mass tagging, the work herein presents a grand scope of protein-based molecular mechanisms involved with ischemic stroke recovery.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0231978