A substitution in the glutathione reductase lowers electron leakage and inflammation in modern humans
Glutathione reductase is a critical enzyme for preventing oxidative stress and maintaining a reduced intracellular environment. Almost all present-day humans carry an amino acid substitution (S232G) in this enzyme relative to apes and Neanderthals. We express the modern human and the ancestral enzymes and show that whereas the activity and stability are unaffected by the amino acid substitution, the ancestral enzyme produces more reactive oxygen species and increases cellular levels of transcripts encoding cytokines. We furthermore show that the ancestral enzyme has been reintroduced into the modern human gene pool by gene flow from Neanderthals and is associated with multiple traits in present-day people, including increased susceptibility for inflammatory-associated disorders and vascular disease.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:8 |
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| Enthalten in: |
Science advances - 8(2022), 1 vom: 07. Jan., Seite eabm1148 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Coppo, Lucia [VerfasserIn] |
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| Links: |
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| Themen: |
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| Anmerkungen: |
Date Revised 02.03.2022 published: Print-Electronic Citation Status PubMed-not-MEDLINE |
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| doi: |
10.1126/sciadv.abm1148 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM335213383 |
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| 520 | |a Glutathione reductase is a critical enzyme for preventing oxidative stress and maintaining a reduced intracellular environment. Almost all present-day humans carry an amino acid substitution (S232G) in this enzyme relative to apes and Neanderthals. We express the modern human and the ancestral enzymes and show that whereas the activity and stability are unaffected by the amino acid substitution, the ancestral enzyme produces more reactive oxygen species and increases cellular levels of transcripts encoding cytokines. We furthermore show that the ancestral enzyme has been reintroduced into the modern human gene pool by gene flow from Neanderthals and is associated with multiple traits in present-day people, including increased susceptibility for inflammatory-associated disorders and vascular disease | ||
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| 700 | 1 | |a Zeberg, Hugo |e verfasserin |4 aut | |
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