Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/81220
Title: iTRAQ Quantitative Clinical Proteomics Revealed Role of Na+K+ -ATPase and Its Correlation with Deamidation in Vascular Dementia
Authors: Adav, Sunil S.
Qian, Jingru
Ang, Yi Lin
Kalaria, Raj N.
Lai, Mitchell K. P.
Chen, Christopher P.
Sze, Siu Kwan
Keywords: dementia; Na+/K+-ATPase; ion channel proteins; iTRAQ; mass spectrometry
Issue Date: 2014
Source: Adav, S. S., Qian, J., Ang, Y. L., Kalaria, R. N., Lai, M. K. P., Chen, C. P., et al. (2014). iTRAQ Quantitative Clinical Proteomics Revealed Role of Na+K+ -ATPase and Its Correlation with Deamidation in Vascular Dementia. Journal of Proteome Research, 13(11), 4635-4646.
Series/Report no.: Journal of Proteome Research
Abstract: Dementia is a major public health burden characterized by impaired cognition and loss of function. There are limited treatment options due to inadequate understanding of its pathophysiology and underlying causative mechanisms. Discovery-driven iTRAQ-based quantitative proteomics techniques were applied on frozen brain samples to profile the proteome from vascular dementia (VaD) and age-matched nondementia controls to elucidate the perturbed pathways contributing to pathophysiology of VaD. The iTRAQ quantitative data revealed significant up-regulation of protein-l-isoaspartate O-methyltransferase and sodium–potassium transporting ATPase, while post-translational modification analysis suggested deamidation of catalytic and regulatory subunits of sodium–potassium transporting ATPase. Spontaneous protein deamidation of labile asparagines, generating abnormal l-isoaspartyl residues, is associated with cell aging and dementia due to Alzheimer’s disease and may be a cause of neurodegeneration. As ion channel proteins play important roles in cellular signaling processes, alterations in their function by deamidation may lead to perturbations in membrane excitability and neuronal function. Structural modeling of sodium–potassium transporting ATPase revealed the close proximity of these deamidated residues to the catalytic site during E2P confirmation. The deamidated residues may disrupt electrostatic interaction during E1 phosphorylation, which may affect ion transport and signal transduction. Our findings suggest impaired regulation and compromised activity of ion channel proteins contribute to the pathophysiology of VaD.
URI: https://hdl.handle.net/10356/81220
http://hdl.handle.net/10220/39155
DOI: 10.1021/pr500754j
Schools: School of Biological Sciences 
Rights: © 2014 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: [http://dx.doi.org/10.1021/pr500754j].
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:SBS Journal Articles

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