SOD1 suppresses maternal hyperglycemia-increased iNOS expression and consequent nitrosative stress in diabetic embryopathy.
Am J Obstet Gynecol
; 206(5): 448.e1-7, 2012 May.
Article
en En
| MEDLINE
| ID: mdl-22425406
ABSTRACT
OBJECTIVE:
Hyperglycemia induces oxidative stress and increases inducible nitric oxide synthase (iNOS) expression. We hypothesized that oxidative stress is responsible for hyperglycemia-induced iNOS expression. STUDYDESIGN:
iNOS-luciferase activities, nitrosylated protein, and lipid peroxidation markers 4-hydroxynonenal and malondialdehyde were determined in parietal yolk sac-2 cells exposed to 5 mmol/L glucose or high glucose (25 mmol/L) with or without copper zinc superoxide dismutase 1 (SOD1) treatment. Levels of iNOS protein and messenger RNA, nitrosylated protein, and cleaved caspase-3 and -8 were assessed in wild-type embryos and SOD1-overexpressing embryos from nondiabetic and diabetic dams.RESULTS:
SOD1 treatment diminished high glucose-induced oxidative stress, as evidenced by 4-hydroxynonenal and malondialdehyde reductions, and it blocked high glucose-increased iNOS expression, iNOS-luciferase activities, and nitrosylated protein. In vivo SOD1 overexpression suppressed hyperglycemia-increased iNOS expression and nitrosylated protein, and it blocked caspase-3 and -8 cleavage.CONCLUSION:
We conclude that oxidative stress induces iNOS expression, nitrosative stress, and apoptosis in diabetic embryopathy.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Superóxido Dismutasa
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Depuradores de Radicales Libres
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Estrés Oxidativo
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Óxido Nítrico Sintasa de Tipo II
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Enfermedades Fetales
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Hiperglucemia
Límite:
Animals
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Pregnancy
Idioma:
En
Revista:
Am J Obstet Gynecol
Año:
2012
Tipo del documento:
Article
País de afiliación:
Estados Unidos