scholarly journals Deletion of Superoxide Dismutase 1 Blunted Inflammatory Aortic Remodeling in Hypertensive Mice under Angiotensin II Infusion

Antioxidants ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 471
Author(s):  
Yasunaga Shiraishi ◽  
Norio Ishigami ◽  
Takehiko Kujiraoka ◽  
Atsushi Sato ◽  
Masanori Fujita ◽  
...  
Keyword(s):  
Superoxide Dismutase ◽  
Angiotensin Ii ◽  
Superoxide Dismutase 1 ◽  
Superoxide Anions ◽  
Vascular Hypertrophy ◽  
Blood Pressures ◽  
Aortic Remodeling ◽  
Deficient Mice ◽  
Cytosolic Sod

Superoxide dismutase (SOD) is an enzyme that catalyzes the dismutation of two superoxide anions (O2·−) into hydrogen peroxide (H2O2) and oxygen (O2) and is generally known to protect against oxidative stress. Angiotensin II (AngII) causes vascular hypertrophic remodeling which is associated with H2O2 generation. The aim of this study is to investigate the role of cytosolic SOD (SOD1) in AngII-induced vascular hypertrophy. We employed C57/BL6 mice (WT) and SOD1 deficient mice (SOD1−/−) with the same background. They received a continuous infusion of saline or AngII (3.2 mg/kg/day) for seven days. The blood pressures were equally elevated at 1.5 times with AngII, however, vascular hypertrophy was blunted in SOD1−/− mice compared to WT mice (WT mice 91.9 ± 1.13 µm versus SOD1−/− mice 68.4 ± 1.41 µm p < 0.001). The elevation of aortic interleukin 6 (IL-6) and phosphorylation of pro-inflammatory STAT3 due to AngII were also blunted in SOD1−/− mice’s aortas. In cultured rat vascular smooth muscle cells (VSMCs), reducing expression of SOD1 with siRNA decreased AngII induced IL-6 release as well as phosphorylation of STAT3. Pre-incubation with polyethylene glycol (PEG)-catalase also attenuated phosphorylation of STAT3 due to AngII. These results indicate that SOD1 in VSMCs plays a role in vascular hypertrophy due to increased inflammation caused by AngII, probably via the production of cytosolic H2O2.

Potential Role of the Porcine Superoxide Dismutase 1 (SOD1) Gene in Pig Reproduction

2013 ◽  
Vol 24 (1) ◽  
pp. 1-9 ◽  
Author(s):  
D. Bjerre ◽  
L. B. Madsen ◽  
T. Mark ◽  
S. Cirera ◽  
K. Larsen ◽  
...  
Keyword(s):  
Superoxide Dismutase ◽  
Potential Role ◽  
Superoxide Dismutase 1 ◽  
Sod1 Gene

scholarly journals The Role of 2% Rebamipide Eye Drops Related to Conjunctival Differentiation in Superoxide Dismutase-1 (Sod1) Knockout Mice

2018 ◽  
Vol 59 (3) ◽  
pp. 1675 ◽  
Author(s):  
Takashi Kojima ◽  
Cem Simsek ◽  
Ayako Igarashi ◽  
Kazue Aoki ◽  
Kazunari Higa ◽  
...  
Keyword(s):  
Superoxide Dismutase ◽  
Knockout Mice ◽  
Eye Drops ◽  
Superoxide Dismutase 1

Survival role of superoxide dismutase 1 on human granulosa luteinized cells in vitroSurvival role of superoxide dismutase 1 on human granulosa luteinized cells in vitro

2011 ◽  
Vol 45 (04) ◽  
pp. 175-181
Author(s):  
J. Dineva ◽  
I. Vangelov ◽  
R. Abrashev ◽  
K. Todorova ◽  
D. Gulenova ◽  
...  
Keyword(s):  
Superoxide Dismutase ◽  
Superoxide Dismutase 1

scholarly journals Oxidation of the Tryptophan 32 Residue of Human Superoxide Dismutase 1 Caused by Its Bicarbonate-dependent Peroxidase Activity Triggers the Non-amyloid Aggregation of the Enzyme

2014 ◽  
Vol 289 (44) ◽  
pp. 30690-30701 ◽  
Author(s):  
Fernando R. Coelho ◽  
Asif Iqbal ◽  
Edlaine Linares ◽  
Daniel F. Silva ◽  
Filipe S. Lima ◽  
...  
Keyword(s):  
Superoxide Dismutase ◽  
Peroxidase Activity ◽  
Oxidation Products ◽  
Superoxide Dismutase 1 ◽  
Amyloid Aggregation ◽  
Post Translational Modifications ◽  
Covalent Dimer ◽  
Als Patients ◽  
Lateral Sclerosis

The role of oxidative post-translational modifications of human superoxide dismutase 1 (hSOD1) in the amyotrophic lateral sclerosis (ALS) pathology is an attractive hypothesis to explore based on several lines of evidence. Among them, the remarkable stability of hSOD1WT and several of its ALS-associated mutants suggests that hSOD1 oxidation may precede its conversion to the unfolded and aggregated forms found in ALS patients. The bicarbonate-dependent peroxidase activity of hSOD1 causes oxidation of its own solvent-exposed Trp32 residue. The resulting products are apparently different from those produced in the absence of bicarbonate and are most likely specific for simian SOD1s, which contain the Trp32 residue. The aims of this work were to examine whether the bicarbonate-dependent peroxidase activity of hSOD1 (hSOD1WT and hSOD1G93A mutant) triggers aggregation of the enzyme and to comprehend the role of the Trp32 residue in the process. The results showed that Trp32 residues of both enzymes are oxidized to a similar extent to hSOD1-derived tryptophanyl radicals. These radicals decayed to hSOD1-N-formylkynurenine and hSOD1-kynurenine or to a hSOD1 covalent dimer cross-linked by a ditryptophan bond, causing hSOD1 unfolding, oligomerization, and non-amyloid aggregation. The latter process was inhibited by tempol, which recombines with the hSOD1-derived tryptophanyl radical, and did not occur in the absence of bicarbonate or with enzymes that lack the Trp32 residue (bovine SOD1 and hSOD1W32F mutant). The results support a role for the oxidation products of the hSOD1-Trp32 residue, particularly the covalent dimer, in triggering the non-amyloid aggregation of hSOD1.

Effect of the reduction of superoxide dismutase 1 and 2 or treatment with α-tocopherol on tumorigenesis in Atm-deficient mice

2006 ◽  
Vol 41 (4) ◽  
pp. 590-600 ◽  
Author(s):  
Laura Erker ◽  
Ralf Schubert ◽  
Sailaja Elchuri ◽  
Ting-Ting Huang ◽  
David Tarin ◽  
...  
Keyword(s):  
Superoxide Dismutase ◽  
Superoxide Dismutase 1 ◽  
Deficient Mice

scholarly journals Guanylyl Cyclase-A Inhibits Angiotensin II Type 2 Receptor-Mediated Pro-Hypertrophic Signaling in the Heart

Endocrinology ◽  
2009 ◽  
Vol 150 (8) ◽  
pp. 3759-3765 ◽  
Author(s):  
Yuhao Li ◽  
Yoshihiko Saito ◽  
Koichiro Kuwahara ◽  
Xianglu Rong ◽  
Ichiro Kishimoto ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Cardiac Hypertrophy ◽  
Guanylyl Cyclase ◽  
Weight Ratio ◽  
Cross Sectional ◽  
Cardiac Phenotype ◽  
At1 Antagonist ◽  
Hypertrophic Signaling ◽  
Deficient Mice

Angiotensin II plays a key role in the development of cardiac hypertrophy. The contribution of the angiotensin II type 1 receptor (AT1) in angiotensin II-induced cardiac hypertrophy is well established, but the role of AT2 signaling remains controversial. Previously, we have shown that natriuretic peptide receptor/guanylyl cyclase-A (GCA) signaling protects the heart from hypertrophy at least in part by inhibiting AT1-mediated pro-hypertrophic signaling. Here, we investigated the role of AT2 in cardiac hypertrophy observed in mice lacking GCA. Real-time RT-PCR and immunoblotting approaches indicated that the cardiac AT2 gene was overexpressed in GCA-deficient mice. Mice lacking AT2 alone did not exhibit an abnormal cardiac phenotype. In contrast, GCA-deficiency-induced increases in heart to body weight ratio, cardiomyocyte cross-sectional area, and collagen accumulation as evidenced by van Gieson staining were attenuated when AT2 was absent. Furthermore, the up-regulated cardiac expression of hypertrophy-related genes in GCA-null animals was also suppressed. Pharmacological blockade of AT2 with PD123319 similarly attenuated cardiac hypertrophy in GCA-deficient mice. In addition, whereas the AT1 antagonist olmesartan attenuated cardiac hypertrophy in GCA-deficient mice, this treatment was without effect on cardiac hypertrophy in GCA/AT2-double null mice, notwithstanding its potent antihypertensive effect in these animals. These results suggest that the interplay of AT2 and AT1 may be important in the development of cardiac hypertrophy. Collectively, our findings support the assertion that GCA inhibits AT2-mediated pro-hypertrophic signaling in heart and offer new insights into endogenous cardioprotective mechanisms during disease pathogenesis.

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