Research output: Contribution to journal › Article › peer-review
Divergent Dimethylarginine Dimethylaminohydrolase Isoenzyme Expression in the Central Nervous System. / Kozlova, Alena A.; Ragavan, Vinitha N.; Jarzebska, Natalia; Lukianova, Iana V.; Bikmurzina, Anastasia E.; Rubets, Elena; Suzuki-Yamamoto, Toshiko; Kimoto, Masumi; Mangoni, Arduino A.; Gainetdinov, Raul R.; Weiss, Norbert; Bauer, Michael; Markov, Alexander G.; Rodionov, Roman N.; Bernhardt, Nadine.
In: Cellular and Molecular Neurobiology, 05.2021.Research output: Contribution to journal › Article › peer-review
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TY - JOUR
T1 - Divergent Dimethylarginine Dimethylaminohydrolase Isoenzyme Expression in the Central Nervous System
AU - Kozlova, Alena A.
AU - Ragavan, Vinitha N.
AU - Jarzebska, Natalia
AU - Lukianova, Iana V.
AU - Bikmurzina, Anastasia E.
AU - Rubets, Elena
AU - Suzuki-Yamamoto, Toshiko
AU - Kimoto, Masumi
AU - Mangoni, Arduino A.
AU - Gainetdinov, Raul R.
AU - Weiss, Norbert
AU - Bauer, Michael
AU - Markov, Alexander G.
AU - Rodionov, Roman N.
AU - Bernhardt, Nadine
N1 - Kozlova, A.A., Ragavan, V.N., Jarzebska, N. et al. Divergent Dimethylarginine Dimethylaminohydrolase Isoenzyme Expression in the Central Nervous System. Cell Mol Neurobiol (2021). https://doi.org/10.1007/s10571-021-01101-7
PY - 2021/5
Y1 - 2021/5
N2 - The endogenous methylated derivative of ʟ-arginine, Nω,Nω′-dimethyl-ʟ-arginine (asymmetric dimethylarginine, ADMA), an independent risk factor in many diseases, inhibits the activity of nitric oxide synthases and, consequently, modulates the availability of nitric oxide. While most studies on the biological role of ADMA have focused on endothelial and inducible nitric oxide synthases modulation and its contribution to cardiovascular, metabolic, and renal diseases, a role in regulating neuronal nitric oxide synthases and pathologies of the central nervous system is less understood. The two isoforms of dimethylarginine dimethylaminohydrolase (DDAH), DDAH1 and DDAH2, are thought to be the main enzymes responsible for ADMA catabolism. A current impediment is limited knowledge on specific tissue and cellular distribution of DDAH enzymes within the brain. In this study, we provide a detailed characterization of the regional and cellular distribution of DDAH1 and DDAH2 proteins in the adult murine and human brain. Immunohistochemical analysis showed a wide distribution of DDAH1, mapping to multiple cell types, while DDAH2 was detected in a limited number of brain regions and exclusively in neurons. Our results provide key information for the investigation of the pathophysiological roles of the ADMA/DDAH system in neuropsychiatric diseases and pave the way for the development of novel selective therapeutic approaches.
AB - The endogenous methylated derivative of ʟ-arginine, Nω,Nω′-dimethyl-ʟ-arginine (asymmetric dimethylarginine, ADMA), an independent risk factor in many diseases, inhibits the activity of nitric oxide synthases and, consequently, modulates the availability of nitric oxide. While most studies on the biological role of ADMA have focused on endothelial and inducible nitric oxide synthases modulation and its contribution to cardiovascular, metabolic, and renal diseases, a role in regulating neuronal nitric oxide synthases and pathologies of the central nervous system is less understood. The two isoforms of dimethylarginine dimethylaminohydrolase (DDAH), DDAH1 and DDAH2, are thought to be the main enzymes responsible for ADMA catabolism. A current impediment is limited knowledge on specific tissue and cellular distribution of DDAH enzymes within the brain. In this study, we provide a detailed characterization of the regional and cellular distribution of DDAH1 and DDAH2 proteins in the adult murine and human brain. Immunohistochemical analysis showed a wide distribution of DDAH1, mapping to multiple cell types, while DDAH2 was detected in a limited number of brain regions and exclusively in neurons. Our results provide key information for the investigation of the pathophysiological roles of the ADMA/DDAH system in neuropsychiatric diseases and pave the way for the development of novel selective therapeutic approaches.
KW - Brain
KW - DDAH1
KW - DDAH2
KW - Human
KW - Mouse
KW - NITRIC-OXIDE SYNTHASE
KW - ASYMMETRIC DIMETHYLARGININE
KW - N-G
KW - IDENTIFICATION
KW - PLASMA
KW - ENDOTHELIAL-CELL HETEROGENEITY
KW - LONG-TERM POTENTIATION
KW - INHIBITOR
KW - METHYLARGININE
KW - CEREBRAL-ISCHEMIA
UR - http://www.scopus.com/inward/record.url?scp=85106252522&partnerID=8YFLogxK
UR - https://www.mendeley.com/catalogue/a9491e07-dea2-3a15-b6a8-c66f210d6110/
U2 - 10.1007/s10571-021-01101-7
DO - 10.1007/s10571-021-01101-7
M3 - Article
AN - SCOPUS:85106252522
JO - Cellular and Molecular Neurobiology
JF - Cellular and Molecular Neurobiology
SN - 0272-4340
ER -
ID: 86120840