Both authors contributed equally to this work.
Pharmacological induction of vascular extracellular superoxide dismutase expression in vivo
Article first published online: 24 DEC 2008
© 2009 The Authors Journal compilation © 2009 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd
Journal of Cellular and Molecular Medicine
Volume 13, Issue 7, pages 1271–1278, July 2009
How to Cite
Oppermann, M., Balz, V., Adams, V., Thao-Vi Dao, V., Bas, M., Suvorava, T. and Kojda, G. (2009), Pharmacological induction of vascular extracellular superoxide dismutase expression in vivo. Journal of Cellular and Molecular Medicine, 13: 1271–1278. doi: 10.1111/j.1582-4934.2008.00627.x
- Issue published online: 30 JUL 2009
- Article first published online: 24 DEC 2008
- Received: September 12, 2008; Accepted: December 11, 2008
- endothelial nitric oxide synthase;
- extracellular superoxide dismutase;
- nitric oxide;
- pentaerythritol tetranitrate
Pentaerythritol tetranitrate (PETN) treatment reduces progression of atherosclerosis and endothelial dysfunction and decreases oxidation of low-density lipoprotein (LDL) in rabbits. These effects are associated with decreased vascular superoxide production, but the underlying molecular mechanisms remain unknown. Previous studies demonstrated that endogenous nitric oxide could regulate the expression of extracellular superoxide dismutase (ecSOD) in conductance vessels in vivo. We investigated the effect of PETN and overexpression of endothelial nitric oxide synthase (eNOS++) on the expression and activity of ecSOD. C57BL/6 mice were randomized to receive placebo or increasing doses of PETN for 4 weeks and eNOS++ mice with a several fold higher endothelial-specific eNOS expression were generated. The expression of ecSOD was determined in the lung and aortic tissue by real-time PCR and Western blot. The ecSOD activity was measured using inhibition of cytochrome C reduction. There was no effect of PETN treatment or eNOS overexpression on ecSOD mRNA in the lung tissue, whereas ecSOD protein expression increased from 2.5-fold to 3.6-fold (P < 0.05) by 6 mg PETN/kg body weight (BW)/day and 60 mg PETN/kg BW/day, respectively. A similar increase was found in aortic homogenates. eNOS++ lung cytosols showed an increase of ecSOD protein level of 142 ± 10.5% as compared with transgene-negative littermates (P < 0.05), which was abolished by Nω-nitro-L-arginine treatment. In each animal group, the increase of ecSOD expression was paralleled by an increase of ecSOD activity. Increased expression and activity of microvascular ecSOD are likely induced by increased bioavailability of vascular nitric oxide. Up-regulation of vascular ecSOD may contribute to the reported antioxidative and anti-atherosclerotic effects of PETN.