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Text
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URL Address
<a href="http://doi.org/10.1016/j.freeradbiomed.2017.10.373" target="_blank" rel="noreferrer noopener">http://doi.org/10.1016/j.freeradbiomed.2017.10.373</a>
Pages
461–469
Volume
113
Dublin Core
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Title
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Increased serotransferrin and ceruloplasmin turnover in diet-controlled patients with type 2 diabetes.
Publisher
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Free radical biology & medicine
Date
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2017
2017-12
Subject
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*Ceruloplasmin; *Deamidation; *Heavy water metabolic labeling; *High resolution mass spectrometry; *Iron metabolism; *LC-MS/MS; *Non-enzymatic glycation; *Oxidative stress; *Protein Processing; *Proteome dynamics; *Serotransferrin; *Type 2 diabetes mellitus; Adult; Amino Acid Sequence; Case-Control Studies; Ceruloplasmin/genetics/*metabolism; Deuterium/metabolism; Diabetes Mellitus; Diabetic; Diet; Female; Gene Expression Regulation; Glycated Hemoglobin A/genetics/metabolism; Glycosylation; Humans; Iron/*metabolism; Isotope Labeling; Male; Middle Aged; Oxidation-Reduction; Oxidative Stress; Post-Translational; Proteolysis; Transferrin/genetics/*metabolism; Type 2/diet therapy/genetics/*metabolism/pathology
Creator
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Golizeh Makan; Lee Kwangwon; Ilchenko Serguei; Osme Abdullah; Bena James; Sadygov Rovshan G; Kashyap Sangeeta R; Kasumov Takhar
Description
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Type 2 diabetes mellitus (T2DM) is associated with oxidative stress and perturbed iron metabolism. Serotransferrin (Trf) and ceruloplasmin (Cp) are two key proteins involved in iron metabolism and anti-oxidant defense. Non-enzymatic glycation and oxidative modification of plasma proteins are known to occur under hyperglycemia and oxidative stress. In this study, shotgun proteomics and (2)H2O-based metabolic labeling were used to characterize post-translational modifications and assess the kinetics of Trf and Cp in T2DM patients and matched controls in vivo. Six early lysine (Amadori) and one advanced arginine glycation were detected in Trf. No glycation, but five asparagine deamidations, were found in Cp. T2DM patients had increased fractional catabolic rates of both Trf and Cp that correlated with HbA1c (p \textless 0.05). The glycated Trf population was subject to an even faster degradation compared to the total Trf pool, suggesting that hyperglycemia contributed to an increased Trf degradation in T2DM patients. Enhanced production of Trf and Cp kept their levels stable. The changes in Trf and Cp turnover were associated with increased systemic oxidative stress without any alteration in iron status in T2DM. These findings can help better understand the potential role of altered Trf and Cp metabolism in the pathogenesis of T2DM and other diseases.
Identifier
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<a href="http://doi.org/10.1016/j.freeradbiomed.2017.10.373" target="_blank" rel="noreferrer noopener">10.1016/j.freeradbiomed.2017.10.373</a>
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Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
*Ceruloplasmin
*Deamidation
*Heavy water metabolic labeling
*High resolution mass spectrometry
*Iron metabolism
*LC-MS/MS
*Non-enzymatic glycation
*Oxidative Stress
*Protein Processing
*Proteome dynamics
*Serotransferrin
*Type 2 diabetes mellitus
2017
Adult
Amino Acid Sequence
Bena James
Case-Control Studies
Ceruloplasmin/genetics/*metabolism
Department of Pharmaceutical Sciences
Deuterium/metabolism
Diabetes Mellitus
Diabetic
Diet
Female
Free radical biology & medicine
Gene Expression Regulation
Glycated Hemoglobin A/genetics/metabolism
Glycosylation
Golizeh Makan
Humans
Ilchenko Serguei
Iron/*metabolism
Isotope Labeling
Kashyap Sangeeta R
Kasumov Takhar
Lee Kwangwon
Male
Middle Aged
NEOMED College of Pharmacy
Osme Abdullah
Oxidation-Reduction
Oxidative Stress
Post-Translational
Proteolysis
Sadygov Rovshan G
Transferrin/genetics/*metabolism
Type 2/diet therapy/genetics/*metabolism/pathology