A multicentric consortium study demonstrates that dimethylarginine dimethylaminohydrolase 2 is not a dimethylarginine dimethylaminohydrolase.
A multicentric consortium study demonstrates that dimethylarginine dimethylaminohydrolase 2 is not a dimethylarginine dimethylaminohydrolase.
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DOI：
10.1038/s41467-023-38467-9
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发表时间：
2023-06-09
影响因子：
16.6
通讯作者：
Rodionov, Roman N.
中科院分区：
文献类型：
--
作者：
Ragavan, Vinitha N.;Nair, Pramod C.;Jarzebska, Natalia;Angom, Ramcharan Singh;Ruta, Luana;Bianconi, Elisa;Grottelli, Silvia;Tararova, Natalia D.;Ryazanskiy, Daniel;Lentz, Steven R.;Tommasi, Sara;Martens-Lobenhoffer, Jens;Suzuki-Yamamoto, Toshiko;Kimoto, Masumi;Rubets, Elena;Chau, Sarah;Chen, Yingjie;Hu, Xinli;Bernhardt, Nadine;Spieth, Peter M.;Weiss, Norbert;Bornstein, Stefan R.;Mukhopadhyay, Debabrata;Bode-Boeger, Stefanie M.;Maas, Renke;Wang, Ying;Macchiarulo, Antonio;Mangoni, Arduino A.;Cellini, Barbara;Rodionov, Roman N.
二甲基精氨酸二甲氨基水解酶1 （DDAH1）通过代谢危险因子不对称二甲基精氨酸（ADMA）来预防心血管疾病。然而，第二个DDAH亚型DDAH2是否直接代谢ADMA的问题仍然没有答案。因此，目前尚不清楚DDAH2是否可能是降低adma治疗的潜在靶点，或者药物开发工作是否应该关注DDAH2在线粒体裂变、血管生成、血管重塑、胰岛素分泌和免疫反应中的已知生理功能。在这里，一个由研究小组组成的国际联盟开始利用硅、体外、细胞培养和小鼠模型来解决这个问题。研究结果一致表明，DDAH2不能代谢ADMA，从而解决了长达20年的争议，并为研究DDAH2的替代功能提供了起点，这些功能与ADMA无关。虽然二甲精氨酸二甲氨基水解酶1 （DDAH1）已知代谢内源性一氧化氮合酶抑制剂不对称二甲基精氨酸（ADMA），但DDAH2的功能仍然存在争议。在这里，作者提出了几条线的证据，证明DDAH2不水解ADMA。
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.
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影响因子：
4.6
作者：
Burdin DV;Kolobov AA;Brocker C;Soshnev AA;Samusik N;Demyanov AV;Brilloff S;Jarzebska N;Martens-Lobenhoffer J;Mieth M;Maas R;Bornstein SR;Bode-Böger SM;Gonzalez F;Weiss N;Rodionov RN
通讯作者：
Rodionov RN
DOI：
10.1073/pnas.0603873103
发表时间：
2006-12-26
影响因子：
11.1
作者：
Duhr, Stefan;Braun, Dieter
通讯作者：
Braun, Dieter
影响因子：
4.9
作者：
Chen W;Wang H;Liu J;Li K
通讯作者：
Li K
DOI：
10.1161/atvbaha.110.222638
发表时间：
2011-07
期刊：
Arteriosclerosis, thrombosis, and vascular biology
影响因子：
--
作者：
Hu X;Atzler D;Xu X;Zhang P;Guo H;Lu Z;Fassett J;Schwedhelm E;Böger RH;Bache RJ;Chen Y
通讯作者：
Chen Y
影响因子：
2.1
作者：
GASTEIGER, J;MARSILI, M
通讯作者：
MARSILI, M