Proteomics

Dataset Information

36

Human holo-transferrin glycation


ABSTRACT: Understanding the effect of glycation on the function of transferrin, the systemic iron transporter, is fundamental to fully grasp the mechanisms leading to the loss of iron homeostasis observed in diabetes mellitus (DM). The spontaneous reaction with protein amino groups is one of the main causes of glucose toxicity, but the site specificity of this reaction is still poorly understood. Unbalance of iron metabolism has long been described in DM patients, and one of the main features is the occurrence of non-transferrin-bound iron in the blood serum. The presence of these toxic iron species is observed, despite low transferrin saturation levels. Here in, an in vitro approach was used to study human holo-transferrin glycation in detail. Holo-transferrin was incubated with increasing concentration of glucose (10; 20; 100 and 500 mM) and glycation sites were identified using nano-reverse phase – liquid chromatography coupled to high resolution mass spectrometry (nLC-MS). Overall 21 glycation hotspots were identified with lysine residues 103, 312 and 380 proving to be the most reactive sites. Glycation specificity was found to be remarkably different from that described for apo-transferrin.

INSTRUMENT(S): LTQ Orbitrap

ORGANISM(S): Homo sapiens  

TISSUE(S): Blood Serum

DISEASE(S): Not Available

SUBMITTER: André Silva  

LAB HEAD: André Moreira Neto da Silva

PROVIDER: PXD009345 | Pride | 2018-05-30

REPOSITORIES: pride

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Publications

Determining the glycation site specificity of human holo-transferrin.

Silva André M N AMN   Coimbra João T S JTS   Castro Maria M MM   Oliveira Ângela    Brás Natércia F NF   Fernandes Pedro A PA   Ramos Maria J MJ   Rangel Maria M  

Journal of inorganic biochemistry 20180526


Understanding the effect of glycation on the function of transferrin, the systemic iron transporter, is fundamental to fully grasp the mechanisms leading to the loss of iron homeostasis observed in diabetes mellitus (DM). The spontaneous reaction with protein amino groups is one of the main causes of glucose toxicity, but the site specificity of this reaction is still poorly understood. Here in, an in vitro approach was used to study human holo-transferrin glycation in detail. Lysine residues 10  ...[more]

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