Heat shock protein 90alpha-dependent translocation of annexin II to the surface of endothelial cells modulates plasmin activity in the diabetic rat aorta.
The goals of this article were (1) to identify cell surface proteins whose expression was regulated by diabetes and (2) to assess their contribution to diabetic complications. We purified heat shock protein 90alpha (Hsp90alpha) from the membrane fraction of high glucose-treated endothelial cells (ECs) as a binding partner for a diabetes-specific phage. Further investigation revealed that high glucose elevated cell surface Hsp90alpha in cultured cells, and that diabetes increased the amount of Hsp90alpha on the luminal surface of the aorta. We also found that high glucose or diabetes promoted the association of Hsp90alpha with annexin II and increased the expression of annexin II on the surface of aortic ECs. Finally, plasmin activity was increased by high glucose or diabetes, and this change was partially reversed with an annexin II antibody. These findings reveal a novel glucose-regulated interaction between Hsp90alpha and annexin II, and raise the possibility that increased expression of annexin II, which promotes the generation of plasmin, is linked to clotting abnormalities associated with the diabetic state.
Schepens Eye Research Institute and Department of Ophthalmology and Harvard Medical School, Boston, Mass 02114, USA.
Hetian
H
Lei
Giulio
G
Romeo
Andrius
A
Kazlauskas
D000328:Adult; D000818:Animals; D017306:Annexin A2 / Q000096:biosynthesis / Q000737:chemistry / Q000276:immunology / Q000502:physiology*; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001011:Aorta / Q000737:chemistry / Q000166:cytology; D002417:Cattle; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D048909:Diabetes Complications; D003920:Diabetes Mellitus / Q000097:blood*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000473:pathology; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D004730:Endothelium, Vascular / Q000473:pathology*; D005341:Fibrinolysin / Q000096:biosynthesis; D005342:Fibrinolysis; D005947:Glucose / Q000494:pharmacology; D018841:HSP90 Heat-Shock Proteins / Q000737:chemistry / Q000502:physiology*; D006801:Humans; D046911:Macromolecular Substances; D008297:Male; D019151:Peptide Library; D025941:Protein Interaction Mapping; D020033:Protein Isoforms / Q000737:chemistry / Q000502:physiology; D021381:Protein Transport; D051381:Rats; D017207:Rats, Sprague-Dawley; D013552:Swine; D019851:Thrombophilia / Q000209:etiology* / Q000378:metabolism
D017306:Annexin A2; D000911:Antibodies, Monoclonal; D018841:HSP90 Heat-Shock Proteins; D046911:Macromolecular Substances; D019151:Peptide Library; D020033:Protein Isoforms; D005341:Fibrinolysin; D005947:Glucose