Mahmood, Sameer Mohammed (2019) Investigation of modified forms of serum C-reactive protein in diabetes mellitus. Doctoral thesis, Keele University.

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Abstract

C-reactive protein (CRP) is known to dissociate to its monomeric subunits (mCRP) in vivo. Furthermore, hyperglycaemia associated with diabetes mellitus (DM) results in glycation of serum proteins to a various extent based on their half-life and glycability. The research described here focuses on modified forms (glycated and monomeric) of the acute phase reactant, CRP, in the serum of DM patients with elevated levels of CRP.
The susceptibility of CRP to the glycation was investigated in vitro. Human CRP was treated using various glucose concentrations and durations, and the glycation status and putative glycation sites determined by mass spectrometry. Analysis of glucose treated samples shows that CRP can be glycated and the glycation extent is both time- and glucose concentration-dependent. Between one and three glucose molecules were found to be condensed on the protein after a period equivalent to its serum half-life, suggesting the possibility of glycation occurring in vivo under high glucose conditions. Among the identified putative glycation sites, K13 was found to be the most susceptible lysine residue in CRP toward glycation.
Human serum samples from participants with DM and elevated CRP levels (>100mg/L, n=24) were investigated for the presence of monomeric and glycated CRP variant. Monomeric CRP was detected in all investigated serum samples, with an average mCRP content of 0.093 mg/L, however no correlation was found between serum levels of mCRP and pCRP. The mCRP showed the ability to reversibly bind phosphocholine, moreover the mCRP displayed a molecular weight of 23,026 Da as determined by mass spectrometry. All 24 diabetic samples were negative for the presence of glycated CRP, suggesting the half-life of the protein is insufficient to cause a detectable level of glycated CRP.

Item Type: Thesis (Doctoral)
Subjects: Q Science > QH Natural history > QH301 Biology
Divisions: Faculty of Natural Sciences > School of Life Sciences
Contributors: Shrive, AK (Thesis advisor)
Greenhough, Trevor (Thesis advisor)
Hart, SR (Thesis advisor)
Tripet, F (Thesis advisor)
Depositing User: Lisa Bailey
Date Deposited: 04 Nov 2019 14:25
Last Modified: 04 Nov 2019 14:25
URI: https://eprints.keele.ac.uk/id/eprint/7131

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