oa Hyperglycemia Regulates Annexin A2-s100a10 Localization In Endothelial Cells

Lara Bou Khzam1, Katherine Hajjar2, Nasrin Mesaeli1 1Weill Cornell Medical College in Qatar, Education City, Doha, Qatar and 2Weill Cornell Medical College New York, USA. Diabetic retinopathy (DR) is a leading cause of legal blindness in working-age individuals resulting in disrupted vascular integrity and pathological retinal angiogenesis in both type I and type II diabetes. Annexin A2 is a regulator of endothelial morphogenesis and plays a role in the modulation of fibrin homeostasis and neoangiogenesis by regulating the generation of plasmin. Heterotetramerization of S100A10 (p11) with Annexin A2 and translocation of this complex to the cell surface is required to modulate the activation of plasmin. We hypothesize that the Annexin A2-p11 system regulates the development of retinal angiogenesis and may be a potential therapeutic target in diabetic retinopathy. Objective of current study is to determine the effect of hyperglycemia on Annexin A2 and p11 expression in endothelial cells. To address this objective we examined effect of high glucose on Annexin A2 and p11 expression in HUVEC cells. Our results illustrated no significant change in the total Annexin A2 protein or mRNA after exposure to different doses of glucose for different times. However, hyperglycemia increased p11 protein expression. To determine weather hyperglycemia affects cellular distribution of Annexin A2 and p11 we used cell surface biotinylation and immunocytochemcial staining (ICC) . Biotinylation studies illustrated an increased cell surface expression of both Annexin A2 and p11 under high-dose glucose conditions. ICC experiments also illustrated cell surface localization of Annexin A2 and p11 following high glucose exposure. Overall our data illustrates a role for high glucose in post-translational regulation of Annexin A2 and p11. Future studies are focused on examining the nature of the post-translational modification in Annexin A2 and p11. Acknowledgment: This work is supported by NPRP No: 6-736-3-187 by QNRF.