Enhancement of glomerular heme oxygenase-1 expression in diabetic rats

An increase in oxidative stress in diabetic subjects is implicated to play a pivotal role in diabetic vascular complications. In response to oxidative stress, antioxidant enzymes are considered to be induced and protect cellu lar functions to keep in vivo homeostasis. However, it remains to be clarif ied whether antioxidant enzymes are induced against oxidative stress especi ally in renal glomeruli at an early stage of diabetes. To answer this quest ion, we examined the gene expression of a variety of antioxidant enzymes in glomeruli isolated from streptozotocin-induced diabetic rats. The mRNA exp ression of antioxidant enzymes such as catalase, glutathione peroxidase, an d CuZn-su-peroxide dismutase, was unaltered in glomeruli of diabetic rats a nd was comparable to control rats. In contrast, the mRNA expression of heme oxygenase-1 (HO-1) was enhanced in glomeruli of diabetic rats as compared with control rats. A treatment with insulin as well as with vitamin E (40 m g/kg body weight every other day, intra-peritoneal injection) normalized th e mRNA expression of HO-1 in the glomeruli of diabetic rats. Immunohistoche mical analysis revealed th;it the up-regulated expression of HO-1 protein w as localized in glomerular cells of diabetic rats. In conclusion, these res ults provide the first evidence that among antioxidant enzymes HO-1 express ion is preferentially increased in diabetic glomeruli. (C) 2001 Elsevier Sc ience Ireland Ltd. All rights reserved.