Enhancement of glomerular heme oxygenase-1 expression in diabetic rats

Diabetes Res Clin Pract. 2001 May;52(2):85-96. doi: 10.1016/s0168-8227(01)00218-2.

Abstract

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 cellular functions to keep in vivo homeostasis. However, it remains to be clarified whether antioxidant enzymes are induced against oxidative stress especially in renal glomeruli at an early stage of diabetes. To answer this question, we examined the gene expression of a variety of antioxidant enzymes in glomeruli isolated from streptozotocin-induced diabetic rats. The mRNA expression of antioxidant enzymes such as catalase, glutathione peroxidase, and CuZn-superoxide dismutase, was unaltered in glomeruli of diabetic rats and 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 mg/kg body weight every other day, intra-peritoneal injection) normalized the mRNA expression of HO-1 in the glomeruli of diabetic rats. Immunohistochemical analysis revealed that the up-regulated expression of HO-1 protein was localized in glomerular cells of diabetic rats. In conclusion, these results provide the first evidence that among antioxidant enzymes HO-1 expression is preferentially increased in diabetic glomeruli.

MeSH terms

  • Animals
  • Catalase / genetics
  • Diabetes Mellitus, Experimental / enzymology*
  • Glutathione Peroxidase / genetics
  • Heme Oxygenase (Decyclizing) / genetics
  • Heme Oxygenase (Decyclizing) / metabolism*
  • Heme Oxygenase-1
  • Immunohistochemistry
  • In Vitro Techniques
  • Kidney Glomerulus / drug effects
  • Kidney Glomerulus / enzymology*
  • Male
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Superoxide Dismutase / genetics
  • Vitamin E / pharmacology

Substances

  • RNA, Messenger
  • Vitamin E
  • Catalase
  • Glutathione Peroxidase
  • Heme Oxygenase (Decyclizing)
  • Heme Oxygenase-1
  • Superoxide Dismutase