Upregulation of caveolin-1 expression is associated with structural modifications of endothelial cells in diabetic lung.
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.
Uyy
Elena
E
Institute of Cellular Biology and Pathology Nicolae Simionescu, 8, BP Hasdeu Street, PO Box 35-14, 050568 Bucharest, Romania.
Antohe
Felicia
F
Ivan
Luminita
L
Haraba
Raluca
R
Radu
Dorel Lucian
DL
Simionescu
Maya
M
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
C495540:CAV1 protein, human; D051242:Caveolin 1; D012333:RNA, Messenger; D002784:Cholesterol; D007703:Peptidyl-Dipeptidase A