Increased nitration and diminished activity of copper/zinc superoxide dismutase in placentas from diabetic rats.
Nitration-induced protein damage in the placenta leads to impaired blood flow and deficient feto-placental exchange in diabetic pregnancies. This work studied the effect of nitric oxide and peroxynitrite on Cu/Zn SOD activity in rat placentas and evaluated whether Cu/Zn SOD is nitrated in the placenta from diabetic rats at mid-gestation. Protein nitration was evaluated by EIA, Cu/Zn SOD activity by inhibition of the epinephrine auto-oxidation, Cu/Zn SOD expression by western blot and specific nitration by immunoprecipitation. This study found higher levels of protein nitration (p < 0.001), diminished Cu/Zn SOD activity and enhanced protein expression (p < 0.01) in placentas from diabetic rats. Placental Cu/Zn SOD activity was inhibited by peroxynitrite (p < 0.01). Besides, nitration of Cu/Zn SOD was elevated in placentas from diabetic rats (p < 0.01). These results show that rat Cu/Zn SOD can be nitrated, a modification that could lead to the depressed activity of this enzyme found in placentas from diabetic rats.
White
Verónica
V
Laboratory of Reproduction and Metabolism, CEFyBO-CONICET, School of Medicine, University of Buenos Aires, Argentina. vernica73@yahoo.com.ar
Capobianco
Evangelina
E
Higa
Romina
R
Martínez
Nora
N
Sosa
María
M
Pustovrh
María C
MC
Jawerbaum
Alicia
A
D000595:Amino Acid Sequence; D000818:Animals; D002417:Cattle; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000378:metabolism*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008969:Molecular Sequence Data; D009569:Nitric Oxide / Q000378:metabolism; D030421:Peroxynitrous Acid / Q000494:pharmacology; D010920:Placenta / Q000187:drug effects / Q000201:enzymology*; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D016415:Sequence Alignment; D013311:Streptozocin; D013482:Superoxide Dismutase / Q000096:biosynthesis*; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
D030421:Peroxynitrous Acid; D009569:Nitric Oxide; C002744:3-nitrotyrosine; D014443:Tyrosine; D013311:Streptozocin; D013482:Superoxide Dismutase