title: Upregulation of caveolin-1 expression is associated with structural modifications of endothelial cells in diabetic lung.
abstract: Diabetes and the associated hyperglycemia affect pulmonary physiology and biochemistry inducing endothelial impairment, as the first step in lung vascular dysfunction. Caveolin-1, a characteristic protein of endothelial caveolae, acts as a scaffolding protein involved in signal transduction, cholesterol homeostasis, and vesicular trafficking. To document the effect of hyperglycemia on lung endothelial cells, we designed experiments on streptozotocin-induced diabetes and on double transgenic diabetic mice and investigated (1) the early morphological changes occurring in endothelial cells, (2) the ACE activity and cholesterol content of caveolae-rich membrane microdomains, and (3) the protein and gene expression of caveolin-1. We provide evidence that in diabetic lung, the endothelial cell displays an increased number of caveolae and enlarged surface area and a well-developed synthetic machinery, changes that correlate with an overall augmented ACE activity and cholesterol content and overexpression (gene and protein) of caveolin-1. Targeting the endothelial cell surface molecules modulated by hyperglycemia, such as caveolin-1 and ACE could be an additional therapeutic strategy in diabetes.
authors.affiliation: Institute of Cellular Biology and Pathology Nicolae Simionescu, 8, BP Hasdeu Street, PO Box 35-14, 050568 Bucharest, Romania.
authors.forename: Elena
authors.initials: E
authors.lastname: Uyy
authors.forename: Felicia
authors.initials: F
authors.lastname: Antohe
authors.forename: Luminita
authors.initials: L
authors.lastname: Ivan
authors.forename: Raluca
authors.initials: R
authors.lastname: Haraba
authors.forename: Dorel Lucian
authors.initials: DL
authors.lastname: Radu
authors.forename: Maya
authors.initials: M
authors.lastname: Simionescu
mesh_terms: D000818:Animals; D051242:Caveolin 1 / Q000235:genetics / Q000378:metabolism*; D002458:Cell Fractionation; D022081:Cell Surface Extensions / Q000648:ultrastructure; D002784:Cholesterol / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000648:ultrastructure; D015870:Gene Expression; D015151:Immunoblotting; D008168:Lung / Q000098:blood supply; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D015854:Up-Regulation
chemical_list: C495540:CAV1 protein, human; D051242:Caveolin 1; D012333:RNA, Messenger; D002784:Cholesterol; D007703:Peptidyl-Dipeptidase A