Increased nitration and diminished activity of copper/zinc superoxide dismutase in placentas from diabetic rats.

WHITE V; CAPOBIANCO E; HIGA,R; MARTÍNEZ N; SOSA M; JAWERBAUM A

FREE RADICAL RESEARCH

TAYLOR & FRANCIS LTD

Lugar: Oxford; Año: 2010 p. 1407 - 1415

1071-5762

Nitrosative and oxidative stress are characteristic features of diabetic pregnancy. Nitrosylation-induced protein damage in the placenta leads to impaired blood flow and deficient feto-placental exchange in diabetic pregnancies. Cu/Zn superoxide dismutase (SOD) is an important enzyme in the defence mechanisms against oxidative damage. In this work, we studied the effect of nitric oxide and peroxynitrite on Cu/Zn SOD activity in rat placentas and evaluated whether Cu/Zn SOD is nitrosylated in the placenta from diabetic rats at midgestation.  The placentas from control and neonatal streptozotocin-induced diabetic pregnant rats were studied on day 13.5 of gestation. Protein nitrosylation was evaluated by EIA, Cu/Zn SOD activity by inhibition of the epinephrine autoxidation, Cu/Zn SOD expression by western blot and specific nitrosylation by immunoprecipitation. We found higher levels of protein nitrosylation (p<0.001) and diminished Cu/Zn SOD activity (p<0.01) in placentas from diabetic rats. Placental Cu/Zn SOD activity was 60% inhibited by peroxynitrite. Cu/Zn SOD expression was enhanced in placental tissues from diabetic rats (p<0.01). Besides, nitrosylation of Cu/Zn SOD was elevated in placentas from diabetic rats (p<0.01). This study demonstrates that maternal diabetes leads to nitrosylation of Cu/Zn SOD, a modification related to the depressed activity of this enzyme in the placenta.