iTRAQ-based quantitative protein expression profiling and MRM verification of markers in type 2 diabetes.
Author | Uppal, , Arushi |
Author | Dennis, Kevin |
Author | Karve, ,Tejaswita |
Author | Blakeslee, , Kenneth |
Author | Kwagyan, John |
Author | Zirie, , Mahmoud |
Author | Younes, Noura |
Author | Ibrahim, Sereen |
Author | Kaur, , Prabhjit |
Author | Rizk, Nasser M |
Author | Cheema, Amrita K |
Available date | 2020-07-21T07:52:09Z |
Publication Date | 2012-11-01 |
Publication Name | Journal of Proteome Research |
Identifier | http://dx.doi.org/10.1021/pr300798z |
Citation | Prabhjit Kaur, Nasser M. Rizk, Sereen Ibrahim, Noura Younes, Arushi Uppal, Kevin Dennis, Tejaswita Karve, Kenneth Blakeslee, John Kwagyan, Mahmoud Zirie, Habtom W. Ressom, and Amrita K. Cheema Journal of Proteome Research 2012 11 (11), 5527-5539 DOI: 10.1021/pr300798z |
Abstract | The pathogenesis of Type 2 diabetes mellitus (T2DM) is complex owing to molecular heterogeneity in the afflicted population. Current diagnostic methods rely on blood glucose measurements, which are noninformative with respect to progression of the disease to other associated pathologies. Thus, predicting the risk and development of T2DM-related complications, such as cardiovascular disease, remains a major challenge. We have used a combination of quantitative methods for characterization of circulating serum biomarkers of T2DM using a cohort of nondiabetic control subjects (n = 76) and patients diagnosed with T2DM (n = 106). In this case-control study, the samples were randomly divided as training and validation data sets. In the first step, iTRAQ (isobaric tagging for relative and absolute quantification) based protein expression profiling was performed for identification of proteins displaying a significant differential expression in the two study groups. Five of these protein markers were selected for validation using multiple reaction-monitoring mass spectrometry (MRM-MS) and further confirmed with Western blot and QPCR analysis. Functional pathway analysis identified perturbations in lipid and small molecule metabolism as well as pathways that lead to disruption of glucose homeostasis and blood coagulation. These putative biomarkers may be clinically useful for subset stratification of T2DM patients as well as for the development of novel therapeutics targeting the specific pathology. |
Sponsor | QNRF-NPRP |
Language | en |
Publisher | American Chemical Society |
Subject | Diabetes Proteomics Biomarkers MRM metabolic syndrome |
Type | Article |
Pagination | 5527-5539 |
Volume Number | 11 |
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Biomedical Sciences [697 items ]