DAF in diabetic patients is subject to glycation/inactivation at its active site residues

作者：Fluckiger Rudolf; Cocuzzi Enzo; Nagaraj Ram H; Shoham Menachem; Kern Timothy S; Medof M Edward^*

来源：Molecular Immunology, 2018, 93: 246-252.

DOI：10.1016/j.molimm.2017.06.036

• DAF
• Glycation
• Diabetes
• Complement
• AGE

Decay accelerating factor (DAF or CD55) is a cell associated C3 and C5 convertase regulator originally described in terms of protection of self-cells from systemic complement but now known to modulate adaptive T cell responses. It is expressed on all cell types. We investigated whether nonenzymatic glycation could impair its function and potentially be relevant to complications of diabetes mellitus and other conditions that result in nonenzymatic glycation including cancer, Alzheimer's disease, and aging. Immunoblots of affinity-purified DAF from erythrocytes of patients with diabetes showed pentosidine, glyoxal-AGEs, carboxymethyllysine, and argpyrimidine. HPLC/MS analyses of glucose modified DAF localized the sites of AGE modifications to 1026 adjacent to 126, K127 at the junction of CCPs2-3 and spatially near R96, and 11196, all identified as being critical for DAF's function. Functional analyses of glucose or ribose treated DAF protein showed profound loss of its regulatory activity. The data argue that de-regulated activation of systemic complement and de-regulated activation of T cells and leukocytes could result from non-enzymatic glycation of DAF.

• 出版日期2018-1