Diabetics are more susceptible to bacterial infection than the general population, potentially due to the inability of diabetics to properly regulate iron, a growth-limiting micronutrient for bacteria.Although non-enzymatic glycosylation of serum proteins occurs in healthy individuals and diabetics alike, it occurs much faster in diabetics due to the increased levels of blood sugar. Serum iron and ferritin levels are higher in diabetics, yet the impact of glycation on proteins involved in iron homeostasis remains unclear. We hypothesize that high serum iron and ferritin levels are a consequence of poor cellular uptake resulting from glycation. While the intracellular, structural and functional role of ferritin is well characterized, the role of serum ferritin is not fully understood, and the consequence of serum ferritin glycation even less so. Recently, Jiang et al. (2009) identified Scavenger Receptor Class A Type 5 (Scara5), as the receptor for L-ferritin, the primary substituent of serum ferritin, and that Scara5 mediates L-ferritin endocytosis.1 In this study, we characterize Scara5 and its interaction with ferritin under glycated and non-glycated conditions in order to gain a better understanding of the relationship between iron transport and glycation. Glucose and fructose are both relevant dietary sugars with different reactivities, while glyoxal is a byproduct of sugar auto-oxidation that is more prevalent in diabetics. While glucose is more likely to modify lysine residues, a-oxoaldehydes like glyoxal usually modify arginine residues. Because ferritin has six lysine and two arginine residues exposed to the surface which potentially play a role inbinding to Scara5, we hypothesize that ferritin glycation will decrease the affinity of the Scara5-ferritin interaction. This would provide a likely mechanism by which iron accumulates in blood, and explain the higher rates of bacterial infection in diabetics.1.      Jiang et al., J. Biol. Chem. 2006  281, 11834-45.

Expression and characterization of ferritin-binding protein, Scara5

247th National Meeting (2014)

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