A multicentric consortium study demonstrates that dimethylarginine dimethylaminohydrolase 2 is not a dimethylarginine dimethylaminohydrolase.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
09 06 2023
09 06 2023
Historique:
received:
05
10
2022
accepted:
27
04
2023
medline:
12
6
2023
pubmed:
10
6
2023
entrez:
9
6
2023
Statut:
epublish
Résumé
Dimethylarginine dimethylaminohydrolase 1 (DDAH1) protects against cardiovascular disease by metabolising the risk factor asymmetric dimethylarginine (ADMA). However, the question whether the second DDAH isoform, DDAH2, directly metabolises ADMA has remained unanswered. Consequently, it is still unclear if DDAH2 may be a potential target for ADMA-lowering therapies or if drug development efforts should focus on DDAH2's known physiological functions in mitochondrial fission, angiogenesis, vascular remodelling, insulin secretion, and immune responses. Here, an international consortium of research groups set out to address this question using in silico, in vitro, cell culture, and murine models. The findings uniformly demonstrate that DDAH2 is incapable of metabolising ADMA, thus resolving a 20-year controversy and providing a starting point for the investigation of alternative, ADMA-independent functions of DDAH2.
Identifiants
pubmed: 37296100
doi: 10.1038/s41467-023-38467-9
pii: 10.1038/s41467-023-38467-9
pmc: PMC10256801
doi:
Substances chimiques
dimethylargininase
EC 3.5.3.18
Amidohydrolases
EC 3.5.-
Arginine
94ZLA3W45F
Nitric Oxide
31C4KY9ESH
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3392Subventions
Organisme : NHLBI NIH HHS
ID : R01 HL140411
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL148339
Pays : United States
Informations de copyright
© 2023. The Author(s).
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