Abstract
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.
Publication types
-
Research Support, Non-U.S. Gov't
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
Animals
-
Anions
-
Antineoplastic Combined Chemotherapy Protocols / pharmacology
-
Aorta / pathology
-
Apoptosis
-
Bilirubin / blood
-
Blotting, Western
-
Cells, Cultured
-
Cyclophosphamide / pharmacology
-
Diabetes Mellitus, Experimental
-
Endothelial Cells / metabolism*
-
Endothelium, Vascular / metabolism
-
Enzyme Inhibitors / pharmacology
-
Glucose / metabolism
-
Heme Oxygenase (Decyclizing) / metabolism
-
Heme Oxygenase (Decyclizing) / physiology*
-
Heme Oxygenase-1
-
Hyperglycemia
-
Luciferases / metabolism
-
Male
-
Metalloporphyrins / pharmacology
-
Oxidative Stress
-
Oxygen / metabolism
-
Plasmids / metabolism
-
Prednisone / pharmacology
-
Procarbazine / pharmacology
-
Promoter Regions, Genetic
-
Rats
-
Rats, Sprague-Dawley
-
Streptozocin
-
Superoxides / metabolism
-
Time Factors
-
Transfection
-
Up-Regulation
-
Vincristine / pharmacology
Substances
-
Anions
-
Enzyme Inhibitors
-
Metalloporphyrins
-
tin mesoporphyrin
-
Superoxides
-
Procarbazine
-
Vincristine
-
Streptozocin
-
Cyclophosphamide
-
Luciferases
-
Heme Oxygenase (Decyclizing)
-
Heme Oxygenase-1
-
Glucose
-
Bilirubin
-
Oxygen
-
Prednisone