Increased serotransferrin and ceruloplasmin turnover in diet-controlled patients with type 2 diabetes

Makan Golizeh, Kwangwon Lee, Serguei Ilchenko, Abdullah Ösme, James Bena, Rovshan Sadygov, Sangeeta Kashyap, Takhar Kasumov

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

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 2H2O-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 < 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.

Original languageEnglish (US)
Pages (from-to)461-469
Number of pages9
JournalFree Radical Biology and Medicine
Volume113
DOIs
StatePublished - Dec 1 2017

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Ceruloplasmin
Transferrin
Nutrition
Medical problems
Type 2 Diabetes Mellitus
Diet
Oxidative stress
Metabolism
Oxidative Stress
Iron
Hyperglycemia
Degradation
Asparagine
Firearms
Post Translational Protein Processing
Oxidants
Proteomics
Labeling
Lysine
Arginine

Keywords

  • Ceruloplasmin
  • Deamidation
  • Heavy water metabolic labeling
  • High resolution mass spectrometry
  • Iron metabolism
  • LC-MS/MS
  • Non-enzymatic glycation
  • Oxidative stress
  • Proteome dynamics
  • Serotransferrin
  • Type 2 diabetes mellitus

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

Cite this

Increased serotransferrin and ceruloplasmin turnover in diet-controlled patients with type 2 diabetes. / Golizeh, Makan; Lee, Kwangwon; Ilchenko, Serguei; Ösme, Abdullah; Bena, James; Sadygov, Rovshan; Kashyap, Sangeeta; Kasumov, Takhar.

In: Free Radical Biology and Medicine, Vol. 113, 01.12.2017, p. 461-469.

Research output: Contribution to journalArticle

Golizeh, Makan ; Lee, Kwangwon ; Ilchenko, Serguei ; Ösme, Abdullah ; Bena, James ; Sadygov, Rovshan ; Kashyap, Sangeeta ; Kasumov, Takhar. / Increased serotransferrin and ceruloplasmin turnover in diet-controlled patients with type 2 diabetes. In: Free Radical Biology and Medicine. 2017 ; Vol. 113. pp. 461-469.
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