Hyperglycemia induces inducible nitric oxide synthase gene expression and consequent nitrosative stress via c-Jun N-terminal kinase activation - 19/08/11
Résumé |
Objective |
Maternal diabetes has an adverse impact on embryonic development. We tested the hypothesis that hyperglycemia-induced c-Jun N-terminal kinases (JNK) 1/2 activation mediates inducible nitric oxide synthase (iNOS) induction.
Study Design |
Levels of iNOS messenger ribonucleic acid (mRNA) and nitrosylated protein were determined in cultured C57BL/6J conceptuses exposed to hyperglycemia (300 mg/dL glucose) and C57BL/6J embryos exposed to streptozotocin-induced diabetes. The iNOS-luciferase activity and endogenous reactive nitrogen species were determined in transfected PYS-2 (mouse teratocarcinoma) cells exposed to hyperglycemia (450 mg/dL glucose).
Results |
Hyperglycemia increased iNOS mRNA, and SP600125, a potent JNK1/2 inhibitor, abolished this effect. Hyperglycemia increased iNOS-luciferase activities, and SP600125 blocked this effect. Diabetes increased iNOS mRNA and jnk2 gene deletion abrogated this effect. Correlated with iNOS gene induction, both hyperglycemia in vitro and diabetes in vivo enhanced the production of reactive nitrogen species and increased protein nitrosylation. The jnk2 gene deletion blocked diabetes-induced protein nitrosylation.
Conclusion |
JNK1/2 activation mediates hyperglycemia-induced iNOS gene expression and consequent nitrosative stress in diabetic embryopathy.
Le texte complet de cet article est disponible en PDF.Key words : c-Jun N-terminal kinase activation, c-Jun N-terminal kinase inhibitor, diabetic embryopathy, inducible nitric oxide synthase gene expression, nitrosative stress
Plan
| Reprints not available from the authors. |
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| This study was supported in part by National Institutes of Health Grant R01DK083243 (P.Y.). P.Y. is a Building Interdisciplinary Research Careers in Women's Health scholar supported by National Institutes of Health Grant K12HD043489 (principal investigator: Dr Patricia Langenberg). |
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| Cite this article as: Yang P, Cao Y, Li H. Hyperglycemia induces inducible nitric oxide synthase gene expression and consequent nitrosative stress via c-Jun N-terminal kinase activation. Am J Obstet Gynecol 2010;203:185.e5-11. |
Vol 203 - N° 2
P. 185.e5-185.e11 - août 2010 Retour au numéro
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