Cobinamide is a strong and versatile antioxidant that overcomes oxidative stress in cells, flies, and diabetic mice
© The Author(s) 2022. Published by Oxford University Press on behalf of National Academy of Sciences..
Increased oxidative stress underlies a variety of diseases, including diabetes. Here, we show that the cobalamin/vitamin B12 analog cobinamide is a strong and multifaceted antioxidant, neutralizing superoxide, hydrogen peroxide, and peroxynitrite, with apparent rate constants of 1.9 × 108, 3.7 × 104, and 6.3 × 106 M-1 s-1, respectively, for cobinamide with the cobalt in the +2 oxidation state. Cobinamide with the cobalt in the +3 oxidation state yielded apparent rate constants of 1.1 × 108 and 8.0 × 102 M-1 s-1 for superoxide and hydrogen peroxide, respectively. In mammalian cells and Drosophila melanogaster, cobinamide outperformed cobalamin and two well-known antioxidants, imisopasem manganese and manganese(III)tetrakis(4-benzoic acid)porphyrin, in reducing oxidative stress as evidenced by: (i) decreased mitochondrial superoxide and return of the mitochondrial membrane potential in rotenone- and antimycin A-exposed H9c2 rat cardiomyocytes; (ii) reduced JNK phosphorylation in hydrogen-peroxide-treated H9c2 cells; (iii) increased growth in paraquat-exposed COS-7 fibroblasts; and (iv) improved survival in paraquat-treated flies. In diabetic mice, cobinamide administered in the animals' drinking water completely prevented an increase in lipid and protein oxidation, DNA damage, and fibrosis in the heart. Cobinamide is a promising new antioxidant that has potential use in diseases with heightened oxidative stress.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:1 |
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| Enthalten in: |
PNAS nexus - 1(2022), 4 vom: 24. Sept., Seite pgac191 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Chang, Stephen [VerfasserIn] |
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| Links: |
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| Themen: |
Antioxidant |
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| Anmerkungen: |
Date Revised 13.02.2024 published: Electronic-eCollection Citation Status PubMed-not-MEDLINE |
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| doi: |
10.1093/pnasnexus/pgac191 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a Increased oxidative stress underlies a variety of diseases, including diabetes. Here, we show that the cobalamin/vitamin B12 analog cobinamide is a strong and multifaceted antioxidant, neutralizing superoxide, hydrogen peroxide, and peroxynitrite, with apparent rate constants of 1.9 × 108, 3.7 × 104, and 6.3 × 106 M-1 s-1, respectively, for cobinamide with the cobalt in the +2 oxidation state. Cobinamide with the cobalt in the +3 oxidation state yielded apparent rate constants of 1.1 × 108 and 8.0 × 102 M-1 s-1 for superoxide and hydrogen peroxide, respectively. In mammalian cells and Drosophila melanogaster, cobinamide outperformed cobalamin and two well-known antioxidants, imisopasem manganese and manganese(III)tetrakis(4-benzoic acid)porphyrin, in reducing oxidative stress as evidenced by: (i) decreased mitochondrial superoxide and return of the mitochondrial membrane potential in rotenone- and antimycin A-exposed H9c2 rat cardiomyocytes; (ii) reduced JNK phosphorylation in hydrogen-peroxide-treated H9c2 cells; (iii) increased growth in paraquat-exposed COS-7 fibroblasts; and (iv) improved survival in paraquat-treated flies. In diabetic mice, cobinamide administered in the animals' drinking water completely prevented an increase in lipid and protein oxidation, DNA damage, and fibrosis in the heart. Cobinamide is a promising new antioxidant that has potential use in diseases with heightened oxidative stress | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a antioxidant | |
| 650 | 4 | |a cobinamide | |
| 650 | 4 | |a diabetes | |
| 650 | 4 | |a oxidative stress | |
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| 700 | 1 | |a China, Shyamsundar Pal |e verfasserin |4 aut | |
| 700 | 1 | |a Kalyanaraman, Hema |e verfasserin |4 aut | |
| 700 | 1 | |a Zhuang, Shunhui |e verfasserin |4 aut | |
| 700 | 1 | |a Chan, Adriano |e verfasserin |4 aut | |
| 700 | 1 | |a Lai, Cassandra |e verfasserin |4 aut | |
| 700 | 1 | |a Radic, Zoran |e verfasserin |4 aut | |
| 700 | 1 | |a Abdel-Rahman, Engy A |e verfasserin |4 aut | |
| 700 | 1 | |a Casteel, Darren E |e verfasserin |4 aut | |
| 700 | 1 | |a Pilz, Renate B |e verfasserin |4 aut | |
| 700 | 1 | |a Ali, Sameh S |e verfasserin |4 aut | |
| 700 | 1 | |a Boss, Gerry R |e verfasserin |4 aut | |
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