Overexpression of human heme oxygenase-1 attenuates endothelial cell sloughing in experimental diabetes.
Heme oxygenase (HO)-1 represents a key defense mechanism against oxidative injury. Hyperglycemia produces oxidative stress and various perturbations of cell physiology. The effect of streptozotocin (STZ)-induced diabetes on aortic HO activity, heme content, the number of circulating endothelial cells, and urinary 8-epi-isoprostane PGF2alpha (8-Epi) levels in control rats and rats overexpressing or underexpressing HO-1 was measured. HO activity was decreased in hyperglycemic rats. Hyperglycemia increased urinary 8-Epi, and this increase was augmented in rats underexpressing HO-1 and diminished in rats overexpressing HO-1. The number of detached endothelial cells and O2- formation increased in diabetic rats and in hyperglycemic animals underexpressing HO-1 and decreased in diabetic animals overexpressing HO-1 compared with controls. These data demonstrate that HO-1 gene transfer in hyperglycemic rats brings about a reduction in O2- production and a decrease in endothelial cell sloughing. Upregulation of HO-1 decreases oxidant production and endothelial cell damage and shedding and may attenuate vascular complications in diabetes.
Department of Pharmacology, New York Medical College, Valhalla, NY 10595, USA. nader_abraham@nymc.edu
Nader G
NG
Abraham
Rita
R
Rezzani
Luigi
L
Rodella
Adam
A
Kruger
Derek
D
Taller
Giovanni
G
Li Volti
Alvin I
AI
Goodman
Attallah
A
Kappas
D000818:Animals; D001011:Aorta / Q000201:enzymology; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D015237:Dinoprost / Q000031:analogs & derivatives* / Q000378:metabolism; D004730:Endothelium, Vascular / Q000201:enzymology* / Q000473:pathology*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics* / Q000378:metabolism*; D051547:Heme Oxygenase-1; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D007150:Immunohistochemistry; D008297:Male; D008565:Membrane Proteins; D030781:Organisms, Genetically Modified; D018384:Oxidative Stress; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley
D008565:Membrane Proteins; C075750:8-epi-prostaglandin F2alpha; D015237:Dinoprost; C496541:HMOX1 protein, human; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; C105245:heme oxygenase-2