congresos y reuniones científicas
Nitric Oxide Synthase and Heme Oxygenase activities in the adrenal cortex of streptozotocin-diabetic Wistar rats
Boston (EEUU)
Congreso; The Endocrine Society’s 88th Annual Meeting – ENDO 2006; 2006
Institución organizadora:
The Endocrine Society
Diabetes causes damage through several mechanisms which include an increase in oxidative stress and nitric oxide (NO) production. In the adrenal cortex, diabetes enhances the synthesis and release of corticosterone, an effect that has been related to some deleterious effects of this disease. Among the responses against such toxic insults is the induction of the enzyme heme oxygenase (HO), which catalyzes the oxidation of heme into biliverdin and carbon monoxide (CO), and the release of iron. Both bilirrubin, produced from biliverdin, and CO have been shown to be cytoprotective. An interaction between the NO synthase (NOS) and HO systems has been suggested in many physiological and pathological conditions. In this sense, it has been demonstrated that increased levels of NO upregulate HO expression and that inhibitors of the HO system inhibit NOS activity. Such interactions could be important in the context of diabetic complications, which entail alterations of the NO pathway. In the present study we have evaluated both NOS and HO systems in the adrenal cortex of streptozotocin (STZ) diabetic rats. Animals: Male Wistar rats were treated with STZ (40 mg/kg ip in three consecutive days). Only those rats exhibiting serum glucose levels over 300 mg/dl were used. Results: Significant increases in both HO-1 mRNA and protein levels were observed after four weeks of diabetes. No differences were observed for HO-2. eNOS and nNOS mRNA and protein levels were also increased in diabetic animals at the same time point. In addition, both enzymatic activities were significantly increased by diabetes (NOS: Control (C): 5.45 0.63 pmol/min/mg vs. STZ: 10.93 0.52 pmol/min/mg, p< 0.001; HO: C: 0.036 0.016 pmol/2h/mg vs. STZ: 0.100 0.012 pmol/2h/mg, p< 0.05). Diabetes also induced increments in the mRNA levels of the L-arginine transporters CAT-2, CD-98 and y+-LAT2, but not CAT-1 in the adrenal cortex. Isolated adrenal cells from diabetic rats produced higher nitrite levels than control ones (C: 2.6 0.3 M vs. STZ: 4.3 0.6 M, p<0.001). Conclusions: Diabetes induces both NOS and HO activities in the adrenal cortex. We suggest that those increments are related to the production of reactive oxygen species triggered by hyperglycemia. As NOS activity is modulated by L-arginine availability the increase in the expression of its transport systems is probably involved in the modulation of this activity.