Regulation of DNA damage and transcriptional output in the vasculature through a cytoglobin-HMGB2 axis.
Carotid artery
Cytoglobin
DNA damage
DNA repair pathways
Hemoglobin
Hydrogen peroxide
Reactive oxygen species
Redox signal
Smooth muscle
Journal
Redox biology
ISSN: 2213-2317
Titre abrégé: Redox Biol
Pays: Netherlands
ID NLM: 101605639
Informations de publication
Date de publication:
09 2023
09 2023
Historique:
received:
29
06
2023
revised:
24
07
2023
accepted:
02
08
2023
medline:
21
8
2023
pubmed:
14
8
2023
entrez:
13
8
2023
Statut:
ppublish
Résumé
Identifying novel regulators of vascular smooth muscle cell function is necessary to further understand cardiovascular diseases. We previously identified cytoglobin, a hemoglobin homolog, with myogenic and cytoprotective roles in the vasculature. The specific mechanism of action of cytoglobin is unclear but does not seem to be related to oxygen transport or storage like hemoglobin. Herein, transcriptomic profiling of injured carotid arteries in cytoglobin global knockout mice revealed that cytoglobin deletion accelerated the loss of contractile genes and increased DNA damage. Overall, we show that cytoglobin is actively translocated into the nucleus of vascular smooth muscle cells through a redox signal driven by NOX4. We demonstrate that nuclear cytoglobin heterodimerizes with the non-histone chromatin structural protein HMGB2. Our results are consistent with a previously unknown function by which a non-erythrocytic hemoglobin inhibits DNA damage and regulates gene programs in the vasculature by modulating the genome-wide binding of HMGB2.
Identifiants
pubmed: 37573836
pii: S2213-2317(23)00239-2
doi: 10.1016/j.redox.2023.102838
pmc: PMC10428073
pii:
doi:
Substances chimiques
Cytoglobin
0
Globins
9004-22-2
HMGB2 Protein
0
Transcription Factors
0
Cygb protein, mouse
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
102838Subventions
Organisme : NHLBI NIH HHS
ID : R01 HL160661
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL142807
Pays : United States
Organisme : NIGMS NIH HHS
ID : P41 GM108538
Pays : United States
Organisme : NHLBI NIH HHS
ID : K01 HL130704
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA233188
Pays : United States
Commentaires et corrections
Type : UpdateOf
Informations de copyright
Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest JJC is a consultant for Thermo Fisher Scientific, 908 Devices, and Seer.
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