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Title: Temporal expression profiling of plasma proteins reveals oxidative stress in early stages of Type 1 Diabetes progression

Abstract

We report that blood markers other than islet autoantibodies are greatly needed to indicate the pancreatic beta cell destruction process as early as possible, and more accurately reflect the progression of Type 1 Diabetes Mellitus (T1D). To this end, a longitudinal proteomic profiling of human plasma using TMT-10plex-based LC-MS/MS analysis was performed to track temporal proteomic changes of T1D patients (n = 11) across 9 serial time points, spanning the period of T1D natural progression, in comparison with those of the matching healthy controls (n = 10). To our knowledge, the current study represents the largest (> 2000 proteins measured) longitudinal expression profiles of human plasma proteome in T1D research. By applying statistical trend analysis on the temporal expression patterns between T1D and controls, and Benjamini-Hochberg procedure for multiple-testing correction, 13 protein groups were regarded as having statistically significant differences during the entire follow-up period. Moreover, 16 protein groups, which play pivotal roles in response to oxidative stress, have consistently abnormal expression trend before seroconversion to islet autoimmunity. Importantly, the expression trends of two key reactive oxygen species-decomposing enzymes, Catalase and Superoxide dismutase were verified independently by ELISA.

Authors:
 [1];  [2];  [2];  [3];  [3]; ORCiD logo [4]
  1. University of North Carolina at Greensboro, North Carolina Research Campus, Kannapolis, NC (United States). Center for Translational Biomedical Research
  2. Pacific Northwest National Lab. (PNNL), Richland, WA (United States). Applied Statistics & Computational Modeling
  3. University of Colorado School of Medicine, Aurora, CO (United States). Barbara Davis Center for Diabetes
  4. University of North Carolina at Greensboro, Greensboro, NC (United States). Department of Chemistry & Biochemistry
Publication Date:
Research Org.:
Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
1413507
Report Number(s):
PNL-SA-125485
Journal ID: ISSN 1874-3919; PII: S1874391917303512; TRN: US1800440
Grant/Contract Number:  
AC05-76RL01830; DK099174; DK114345
Resource Type:
Accepted Manuscript
Journal Name:
Journal of Proteomics
Additional Journal Information:
Journal Volume: 172; Journal Issue: C; Journal ID: ISSN 1874-3919
Publisher:
Elsevier
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; 60 APPLIED LIFE SCIENCES; Temporal proteome change; Type 1 Diabetes; TMT10; Pediatric plasma proteome; Longitudinal profiling; Oxidative stress

Citation Formats

Liu, Chih-Wei, Bramer, Lisa, Webb-Robertson, Bobbie-Jo, Waugh, Kathleen, Rewers, Marian J., and Zhang, Qibin. Temporal expression profiling of plasma proteins reveals oxidative stress in early stages of Type 1 Diabetes progression. United States: N. p., 2017. Web. https://doi.org/10.1016/J.JPROT.2017.10.004.
Liu, Chih-Wei, Bramer, Lisa, Webb-Robertson, Bobbie-Jo, Waugh, Kathleen, Rewers, Marian J., & Zhang, Qibin. Temporal expression profiling of plasma proteins reveals oxidative stress in early stages of Type 1 Diabetes progression. United States. https://doi.org/10.1016/J.JPROT.2017.10.004
Liu, Chih-Wei, Bramer, Lisa, Webb-Robertson, Bobbie-Jo, Waugh, Kathleen, Rewers, Marian J., and Zhang, Qibin. Sat . "Temporal expression profiling of plasma proteins reveals oxidative stress in early stages of Type 1 Diabetes progression". United States. https://doi.org/10.1016/J.JPROT.2017.10.004. https://www.osti.gov/servlets/purl/1413507.
@article{osti_1413507,
title = {Temporal expression profiling of plasma proteins reveals oxidative stress in early stages of Type 1 Diabetes progression},
author = {Liu, Chih-Wei and Bramer, Lisa and Webb-Robertson, Bobbie-Jo and Waugh, Kathleen and Rewers, Marian J. and Zhang, Qibin},
abstractNote = {We report that blood markers other than islet autoantibodies are greatly needed to indicate the pancreatic beta cell destruction process as early as possible, and more accurately reflect the progression of Type 1 Diabetes Mellitus (T1D). To this end, a longitudinal proteomic profiling of human plasma using TMT-10plex-based LC-MS/MS analysis was performed to track temporal proteomic changes of T1D patients (n = 11) across 9 serial time points, spanning the period of T1D natural progression, in comparison with those of the matching healthy controls (n = 10). To our knowledge, the current study represents the largest (> 2000 proteins measured) longitudinal expression profiles of human plasma proteome in T1D research. By applying statistical trend analysis on the temporal expression patterns between T1D and controls, and Benjamini-Hochberg procedure for multiple-testing correction, 13 protein groups were regarded as having statistically significant differences during the entire follow-up period. Moreover, 16 protein groups, which play pivotal roles in response to oxidative stress, have consistently abnormal expression trend before seroconversion to islet autoimmunity. Importantly, the expression trends of two key reactive oxygen species-decomposing enzymes, Catalase and Superoxide dismutase were verified independently by ELISA.},
doi = {10.1016/J.JPROT.2017.10.004},
journal = {Journal of Proteomics},
number = C,
volume = 172,
place = {United States},
year = {2017},
month = {10}
}

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