Journal article
A multicentric consortium study demonstrates that dimethylarginine dimethylaminohydrolase 2 is not a dimethylarginine dimethylaminohydrolase
Nature communications, Vol.14(1), 3392
06/09/2023
DOI: 10.1038/s41467-023-38467-9
PMCID: PMC10256801
PMID: 37296100
Abstract
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.
While dimethylarginine dimethylaminohydrolase 1 (DDAH1) is known to metabolize the endogenous inhibitor of nitric oxide synthases, asymmetric dimethylarginine (ADMA), the function of DDAH2 has remained controversial. Here, the authors present several lines of evidence that DDAH2 does not hydrolyze ADMA.
Details
- Title: Subtitle
- A multicentric consortium study demonstrates that dimethylarginine dimethylaminohydrolase 2 is not a dimethylarginine dimethylaminohydrolase
- Creators
- Vinitha N. Ragavan - Dresden, Germany Adelaide, SA AustraliaPramod C. Nair - Adelaide, SA Australia Adelaide, SA Australia Adelaide, SA Australia Adelaide, SA AustraliaNatalia Jarzebska - Dresden, GermanyRamcharan Singh Angom - Jacksonville, FL USALuana Ruta - via del Liceo 1, Perugia, ItalyElisa Bianconi - via del Liceo 1, Perugia, ItalySilvia Grottelli - P.le L. Sevari 1, Perugia, ItalyNatalia D. Tararova - DAPCEL, Inc., Cleveland, OH USADaniel Ryazanskiy - DAPCEL, Inc., Cleveland, OH USASteven R. Lentz - Iowa City, IA USASara Tommasi - Adelaide, SA AustraliaJens Martens-Lobenhoffer - Magdeburg, GermanyToshiko Suzuki-Yamamoto - Okayama, JapanMasumi Kimoto - Okayama, JapanElena Rubets - Dresden, GermanySarah Chau - Rochester, NY USAYingjie Chen - Jackson Memorial HospitalXinli Hu - Beijing, ChinaNadine Bernhardt - Dresden, GermanyPeter M. Spieth - Dresden, GermanyNorbert Weiss - Dresden, GermanyStefan R. Bornstein - Dresden, Germany London, UKDebabrata Mukhopadhyay - Jacksonville, FL USAStefanie M. Bode-Böger - Magdeburg, GermanyRenke Maas - Erlangen, Germany Erlangen, GermanyYing Wang - Rochester, NY USAAntonio Macchiarulo - via del Liceo 1, Perugia, ItalyArduino A. Mangoni - Adelaide, SA AustraliaBarbara Cellini - P.le L. Sevari 1, Perugia, ItalyRoman N. Rodionov - Dresden, Germany Adelaide, SA Australia
- Resource Type
- Journal article
- Publication Details
- Nature communications, Vol.14(1), 3392
- DOI
- 10.1038/s41467-023-38467-9
- PMID
- 37296100
- PMCID
- PMC10256801
- NLM abbreviation
- Nat Commun
- eISSN
- 2041-1723
- Publisher
- Nature Publishing Group UK
- Grant note
- ; DAAD 57173983 / ; HL140411; HL148339 / ; F/24/17 / ;
- Language
- English
- Date published
- 06/09/2023
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984430332802771
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