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

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

Golizeh Makan; Lee Kwangwon; Ilchenko Serguei; Osme Abdullah; Bena James; Sadygov Rovshan G; Kashyap Sangeeta R; Kasumov Takhar

Free radical biology & medicine

2017

2017-12

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.

*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

Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).

461–469

113