Please use this identifier to cite or link to this item:
Title: Quantitative neuroproteomics of an in vivo rodent model of focal cerebral ischemia/reperfusion injury reveals a temporal regulation of novel pathophysiological molecular markers
Authors: Datta, Arnab
Jingru, Qian
Khor, Tze Hsin
Teo, Muh Tyng
Heese, Klaus
Sze, Siu Kwan
Keywords: DRNTU::Science::Biological sciences
Issue Date: 2011
Source: Datta, A., Qian, J., Khor, T. H., Teo, M. T., Heese, K., & Sze, S. K. (2011). Quantitative neuroproteomics of an in vivo rodent model of focal cerebral ischemia/reperfusion injury reveals a temporal regulation of novel pathophysiological molecular markers. Journal of proteome research, 10(11), 5199–5213.
Series/Report no.: Journal of proteome research
Abstract: Cerebral ischemia or stroke, an acute neurological injury lacking an effective therapy, is the second leading cause of death globally. The unmet need in stroke research is to identify viable targets and to understand their interplay during the temporal evolution of ischemia/reperfusion (I/R) injury. Here we report a temporal signature of the ischemic hemisphere revealed by the isobaric tag for relative and absolute quantification (iTRAQ)-based 2D-LC–MS/MS strategy in an in vivo middle cerebral artery occlusion (MCAO) model of focal cerebral I/R injury. To recapitulate clinical stroke, two hours of MCAO was followed by 0, 4, and 24 h of reperfusion to capture ischemia with an acute and subacute durations of reperfusion injury. The subsequent iTRAQ experiment identified 2242 proteins from the ischemic hemisphere with <1.0% false discovery rate. Data mining revealed that (1) about 2.7% of detected proteins were temporally perturbed having an involvement in the energy metabolism (Pygb, Atp5b), glutamate excitotoxicity (Slc1a3, Glud1), neuro-inflammation (Tf, C3, Alb), and cerebral plasticity (Gfap, Vim, Gap43); (2) astrocytes participated actively in the neurometabolic coupling underlining the importance of a cerebro-protective rather than a neuro-protective approach; and (3) hyper-acute yet progressive opening of the blood brain barrier (BBB), accompanied by stimulation of an innate immune response and late activation of a regenerative response, which provides an extended therapeutic window for intervention. Several regulated proteins (Caskin1, Shank3, Kpnb1, Uchl1, Mtap6, Epb4.1l1, Apba1, and Ube1x) novel in the context of stroke were also discovered. In conclusion, our result supports a dynamic multitarget therapy rather than the traditional approach of a unilateral and sustained modulation of a single target to address the phasic regulation of an ischemic proteome.
DOI: 10.1021/pr200673y
Rights: © 2011 American Chemical Society. This is the author created version of a work that has been peer reviewed and accepted for publication by Journal of proteome research, American Chemical Society. It incorporates referee’s comments but changes resulting from the publishing process, such as copyediting, structural formatting, may not be reflected in this document. The published version is available at: [DOI:].
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:SBS Journal Articles

Files in This Item:
File Description SizeFormat 
Quantitative Neuroproteomics of an In Vivo Rodent Model of Focal Cerebral Ischemia.pdf1.15 MBAdobe PDFThumbnail

Citations 10

Updated on Jan 26, 2023

Web of ScienceTM
Citations 10

Updated on Feb 4, 2023

Page view(s) 10

Updated on Feb 5, 2023

Download(s) 5

Updated on Feb 5, 2023

Google ScholarTM




Items in DR-NTU are protected by copyright, with all rights reserved, unless otherwise indicated.