Limits...
Pharmacological induction of vascular extracellular superoxide dismutase expression in vivo.

Oppermann M, Balz V, Adams V, Dao VT, Bas M, Suvorava T, Kojda G - J. Cell. Mol. Med. (2008)

Bottom Line: These effects are associated with decreased vascular superoxide production, but the underlying molecular mechanisms remain unknown.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 N(omega)-nitro-L-arginine treatment.Up-regulation of vascular ecSOD may contribute to the reported antioxidative and anti-atherosclerotic effects of PETN.

View Article: PubMed Central - PubMed

Affiliation: Institute for Pharmacology and Clinical Pharmacology, Heinrich-Heine-University, Duesseldorf, Germany.

ABSTRACT
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 N(omega)-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.

Show MeSH

Related in: MedlinePlus

ecSOD activity. (A) The activity of extracellular superoxide dismu-tase (ecSOD) in lung tissue of eNOS++ mice was significantly increased compared with eNOSn mice (*=P < 0.05). (B) Treatment of C57Bl/6 mice with 6 or 60 mg/kg/day pentaerythritol tetranitrate (PETN-6 or PETN-60, respectively) similarly resulted in increased activities compared with control mice (PETN-0). *=P < 0.05 versus PETN-0.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC4496141&req=5

fig04: ecSOD activity. (A) The activity of extracellular superoxide dismu-tase (ecSOD) in lung tissue of eNOS++ mice was significantly increased compared with eNOSn mice (*=P < 0.05). (B) Treatment of C57Bl/6 mice with 6 or 60 mg/kg/day pentaerythritol tetranitrate (PETN-6 or PETN-60, respectively) similarly resulted in increased activities compared with control mice (PETN-0). *=P < 0.05 versus PETN-0.

Mentions: Changes in ecSOD activity paralleled changes in ecSOD expression (n= 7, P < 0.0001, anova; Fig. 4A). In the lungs of the PETN-treated mice, the ecSOD activity was 24.2 ± 2.23 U/mg (PETN-6, n= 7, P < 0.05, post-hoc analysis) and 37.3 ± 2.77 U/mg (PETN-60, n= 6, P < 0.01, post-hoc analysis) compared with the ecSOD activity of 16.1 ± 1.95 U/mg in PETN-0 mice. Likewise, the ecSOD activity was significantly increased in eNOS++ mice (63.5 ± 4.24 U/mg, n= 6) compared with eNOSn mice (51.3 ± 2.95 U/mg, n= 6, P= 0.0401; Fig. 4B).


Pharmacological induction of vascular extracellular superoxide dismutase expression in vivo.

Oppermann M, Balz V, Adams V, Dao VT, Bas M, Suvorava T, Kojda G - J. Cell. Mol. Med. (2008)

ecSOD activity. (A) The activity of extracellular superoxide dismu-tase (ecSOD) in lung tissue of eNOS++ mice was significantly increased compared with eNOSn mice (*=P < 0.05). (B) Treatment of C57Bl/6 mice with 6 or 60 mg/kg/day pentaerythritol tetranitrate (PETN-6 or PETN-60, respectively) similarly resulted in increased activities compared with control mice (PETN-0). *=P < 0.05 versus PETN-0.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4496141&req=5

fig04: ecSOD activity. (A) The activity of extracellular superoxide dismu-tase (ecSOD) in lung tissue of eNOS++ mice was significantly increased compared with eNOSn mice (*=P < 0.05). (B) Treatment of C57Bl/6 mice with 6 or 60 mg/kg/day pentaerythritol tetranitrate (PETN-6 or PETN-60, respectively) similarly resulted in increased activities compared with control mice (PETN-0). *=P < 0.05 versus PETN-0.
Mentions: Changes in ecSOD activity paralleled changes in ecSOD expression (n= 7, P < 0.0001, anova; Fig. 4A). In the lungs of the PETN-treated mice, the ecSOD activity was 24.2 ± 2.23 U/mg (PETN-6, n= 7, P < 0.05, post-hoc analysis) and 37.3 ± 2.77 U/mg (PETN-60, n= 6, P < 0.01, post-hoc analysis) compared with the ecSOD activity of 16.1 ± 1.95 U/mg in PETN-0 mice. Likewise, the ecSOD activity was significantly increased in eNOS++ mice (63.5 ± 4.24 U/mg, n= 6) compared with eNOSn mice (51.3 ± 2.95 U/mg, n= 6, P= 0.0401; Fig. 4B).

Bottom Line: These effects are associated with decreased vascular superoxide production, but the underlying molecular mechanisms remain unknown.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 N(omega)-nitro-L-arginine treatment.Up-regulation of vascular ecSOD may contribute to the reported antioxidative and anti-atherosclerotic effects of PETN.

View Article: PubMed Central - PubMed

Affiliation: Institute for Pharmacology and Clinical Pharmacology, Heinrich-Heine-University, Duesseldorf, Germany.

ABSTRACT
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 N(omega)-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.

Show MeSH
Related in: MedlinePlus