Heme oxygenase-1 prevents superoxide anion-associated endothelial cell sloughing in diabetic rats.
Heme oxygenase-1 (HO-1) represents a key defense mechanism against oxidative injury. Hyperglycemia has been linked to increased oxidative stress, leading to endothelial dysfunction, delayed cell replication, and enhanced apoptosis. The effect of streptozotocin (STZ)-induced diabetes on HO activity, HO-1 promoter activity, superoxide anion (O*-2, and the number of circulating endothelial cells was measured. The expression of HO-1/HO-2 protein was unchanged, but HO activity was decreased in aortas of diabetic rats compared with control (p < 0.05). High glucose decreased HO-1 promoter activity (p < 0.05). Hyperglycemia increased O*-2 and this increase was augmented with HO-1 inhibition and diminished with HO-1 upregulation (p < 0.05). Circulating endothelial cells were significantly higher in diabetic rats and were decreased or increased with administration of the HO-1 inducer (CoPP) or inhibitor (SnMP), respectively (p<0.05). In conclusion, HO-1 upregulation in diabetic rats brings about an increase in serum bilirubin, a reduction in O*-2 production, and a decrease in endothelial cell sloughing.
Quan
Shou
S
Department of Pharmacology, New York Medical College, Valhalla, NY, USA.
Kaminski
Pawel M
PM
Yang
Liming
L
Morita
Toshisuke
T
Inaba
Muneo
M
Ikehara
Susumu
S
Goodman
Alvin I
AI
Wolin
Michael S
MS
Abraham
Nader G
NG
D000818:Animals; D000838:Anions; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology; D001011:Aorta / Q000473:pathology; D017209:Apoptosis; D001663:Bilirubin / Q000097:blood; D015153:Blotting, Western; D002478:Cells, Cultured; D003520:Cyclophosphamide / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental; D042783:Endothelial Cells / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism / Q000502:physiology*; D051547:Heme Oxygenase-1; D006943:Hyperglycemia; D008156:Luciferases / Q000378:metabolism; D008297:Male; D008665:Metalloporphyrins / Q000494:pharmacology; D018384:Oxidative Stress; D010100:Oxygen / Q000378:metabolism; D010957:Plasmids / Q000378:metabolism; D011241:Prednisone / Q000494:pharmacology; D011344:Procarbazine / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D051381:Rats; D017207:Rats, Sprague-Dawley; D013311:Streptozocin; D013481:Superoxides / Q000378:metabolism; D013997:Time Factors; D014162:Transfection; D015854:Up-Regulation; D014750:Vincristine / Q000494:pharmacology
D000838:Anions; D004791:Enzyme Inhibitors; D008665:Metalloporphyrins; C055421:tin mesoporphyrin; D013481:Superoxides; D011344:Procarbazine; D014750:Vincristine; D013311:Streptozocin; D003520:Cyclophosphamide; D008156:Luciferases; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; D005947:Glucose; D001663:Bilirubin; D010100:Oxygen; D011241:Prednisone