The carbonylation and covalent dimerization of human superoxide dismutase 1 caused by its bicarbonate-dependent peroxidase activity is inhibited by the radical scavenger tempol

2013 ◽  
Vol 455 (1) ◽  
pp. 37-46 ◽  
Author(s):  
Raphael F. Queiroz ◽  
Verônica Paviani ◽  
Fernando R. Coelho ◽  
Emerson F. Marques ◽  
Paolo Di Mascio ◽  
...  
Keyword(s):  
Superoxide Dismutase ◽  
Peroxidase Activity ◽  
Radical Scavenger ◽  
Superoxide Dismutase 1 ◽  
Carbonate Radical ◽  
Covalent Dimerization

The nitroxide tempol inhibited the carbonylation and covalent dimerization of human superoxide dismutase 1 caused by its bicarbonate-dependent peroxidase activity. Tempol acted by scavenging the produced carbonate radical and by recombining with hSOD1-Trp32• radicals as indicated by MS/MS evidence.

scholarly journals Quantification of carbonate radical formation by the bicarbonate-dependent peroxidase activity of superoxide dismutase 1 using pyrogallol red bleaching

Redox Biology ◽  
2019 ◽  
Vol 24 ◽  
pp. 101207 ◽  
Author(s):  
Juan David Figueroa ◽  
Eduardo Fuentes-Lemus ◽  
Eva Dorta ◽  
Victoria Melin ◽  
Javiera Cortés-Ríos ◽  
...  
Keyword(s):  
Superoxide Dismutase ◽  
Peroxidase Activity ◽  
Radical Formation ◽  
Superoxide Dismutase 1 ◽  
Carbonate Radical ◽  
Pyrogallol Red

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.

Ascorbic acid and CoQ10 ameliorate the reproductive ability of superoxide dismutase 1-deficient female mice†

2019 ◽  
Author(s):  
Naoki Ishii ◽  
Takujiro Homma ◽  
Jaeyong Lee ◽  
Hikaru Mitsuhashi ◽  
Ken-ichi Yamada ◽  
...  
Keyword(s):  
Ascorbic Acid ◽  
Superoxide Dismutase ◽  
Coenzyme Q10 ◽  
Knockout Mice ◽  
Knockout Mouse ◽  
Superoxide Dismutase 1 ◽  
Wild Type ◽  
Positive Effects ◽  
Reproductive Ability ◽  
Ascorbic Acid Supplementation

Abstract Superoxide dismutase 1 suppresses oxidative stress within cells by decreasing the levels of superoxide anions. A dysfunction of the ovary and/or an aberrant production of sex hormones are suspected causes for infertility in superoxide dismutase 1-knockout mice. We report on attempts to rescue the infertility in female knockout mice by providing two antioxidants, ascorbic acid and/or coenzyme Q10, as supplements in the drinking water of the knockout mice after weaning and on an investigation of their reproductive ability. On the first parturition, 80% of the untreated knockout mice produced smaller litter sizes compared with wild-type mice (average 2.8 vs 7.3 pups/mouse), and supplementing with these antioxidants failed to improve these litter sizes. However, in the second parturition of the knockout mice, the parturition rate was increased from 18% to 44–75% as the result of the administration of antioxidants. While plasma levels of progesterone at 7.5 days of pregnancy were essentially the same between the wild-type and knockout mice and were not changed by the supplementation of these antioxidants, sizes of corpus luteum cells, which were smaller in the knockout mouse ovaries after the first parturition, were significantly ameliorated in the knockout mouse with the administration of the antioxidants. Moreover, the impaired vasculogenesis in uterus/placenta was also improved by ascorbic acid supplementation. We thus conclude that ascorbic acid and/or coenzyme Q10 are involved in maintaining ovarian and uterus/placenta homeostasis against insults that are augmented during pregnancy and that their use might have positive effects in terms of improving female fertility.

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