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 <f>(p<0.05)</f>. High glucose decreased HO-1 promoter activity <f>(p<0.05)</f>. Hyperglycemia increased O⋅−2 and this increase was augmented with HO-1 inhibition and diminished with HO-1 upregulation <f>(p<0.05)</f>. 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 <f>(p<0.05)</f>. 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. [Copyright &y& Elsevier]