Dimethylarginine dimethylaminohydrolase-1 transgenic mice are not protected from ischemic stroke.
Methylated arginines are endogenous analogues of L-arginine, the substrate for nitric oxide (NO) synthase. Asymmetric dimethylarginine (ADMA) interferes with NO formation, causing endothelial dysfunction. ADMA is a predictor of cardiovascular events and mortality in humans. It is eliminated primaril...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2009-10-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC2753663?pdf=render |
| _version_ | 1818270257379278848 |
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| author | Frank Leypoldt Chi-Un Choe Mathias Gelderblom Eike-Christin von Leitner Dorothee Atzler Edzard Schwedhelm Christian Gerloff Karsten Sydow Rainer H Böger Tim Magnus |
| author_facet | Frank Leypoldt Chi-Un Choe Mathias Gelderblom Eike-Christin von Leitner Dorothee Atzler Edzard Schwedhelm Christian Gerloff Karsten Sydow Rainer H Böger Tim Magnus |
| author_sort | Frank Leypoldt |
| collection | DOAJ |
| description | Methylated arginines are endogenous analogues of L-arginine, the substrate for nitric oxide (NO) synthase. Asymmetric dimethylarginine (ADMA) interferes with NO formation, causing endothelial dysfunction. ADMA is a predictor of cardiovascular events and mortality in humans. It is eliminated primarily by enzymatic activity of dimethylarginine dimethylaminohydrolase (DDAH).We investigated whether human DDAH-1 (hDDAH-1) transgenicity protects from ischemic tissue damage in temporary middle cerebral artery occlusion (tMCAO) in mice. Infarct sizes did not significantly differ between hDDAH-1 transgenic (TG) mice and wild-type littermates (WT). As expected, ADMA plasma concentrations were significantly decreased, cerebral hDDAH expression and protein significantly increased in transgenic animals. Interestingly, neither brain tissue DDAH activity nor ADMA concentrations were different between TG and WT mice. In contrast, muscular DDAH activity was generally lower than in brain but significantly increased in TG mice.Our study demonstrates that hDDAH-1 transgenic mice are not protected from ischemic cerebral tissue damage in tMCAO. This lack of protection is due to high basal cerebral DDAH activity, which is not further increasable by transgenic overexpression of DDAH. |
| first_indexed | 2024-12-12T21:07:24Z |
| format | Article |
| id | doaj.art-49743f1ff81741f396eb1f09bcee7440 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-12T21:07:24Z |
| publishDate | 2009-10-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-49743f1ff81741f396eb1f09bcee74402022-12-22T00:11:59ZengPublic Library of Science (PLoS)PLoS ONE1932-62032009-10-01410e733710.1371/journal.pone.0007337Dimethylarginine dimethylaminohydrolase-1 transgenic mice are not protected from ischemic stroke.Frank LeypoldtChi-Un ChoeMathias GelderblomEike-Christin von LeitnerDorothee AtzlerEdzard SchwedhelmChristian GerloffKarsten SydowRainer H BögerTim MagnusMethylated arginines are endogenous analogues of L-arginine, the substrate for nitric oxide (NO) synthase. Asymmetric dimethylarginine (ADMA) interferes with NO formation, causing endothelial dysfunction. ADMA is a predictor of cardiovascular events and mortality in humans. It is eliminated primarily by enzymatic activity of dimethylarginine dimethylaminohydrolase (DDAH).We investigated whether human DDAH-1 (hDDAH-1) transgenicity protects from ischemic tissue damage in temporary middle cerebral artery occlusion (tMCAO) in mice. Infarct sizes did not significantly differ between hDDAH-1 transgenic (TG) mice and wild-type littermates (WT). As expected, ADMA plasma concentrations were significantly decreased, cerebral hDDAH expression and protein significantly increased in transgenic animals. Interestingly, neither brain tissue DDAH activity nor ADMA concentrations were different between TG and WT mice. In contrast, muscular DDAH activity was generally lower than in brain but significantly increased in TG mice.Our study demonstrates that hDDAH-1 transgenic mice are not protected from ischemic cerebral tissue damage in tMCAO. This lack of protection is due to high basal cerebral DDAH activity, which is not further increasable by transgenic overexpression of DDAH.http://europepmc.org/articles/PMC2753663?pdf=render |
| spellingShingle | Frank Leypoldt Chi-Un Choe Mathias Gelderblom Eike-Christin von Leitner Dorothee Atzler Edzard Schwedhelm Christian Gerloff Karsten Sydow Rainer H Böger Tim Magnus Dimethylarginine dimethylaminohydrolase-1 transgenic mice are not protected from ischemic stroke. PLoS ONE |
| title | Dimethylarginine dimethylaminohydrolase-1 transgenic mice are not protected from ischemic stroke. |
| title_full | Dimethylarginine dimethylaminohydrolase-1 transgenic mice are not protected from ischemic stroke. |
| title_fullStr | Dimethylarginine dimethylaminohydrolase-1 transgenic mice are not protected from ischemic stroke. |
| title_full_unstemmed | Dimethylarginine dimethylaminohydrolase-1 transgenic mice are not protected from ischemic stroke. |
| title_short | Dimethylarginine dimethylaminohydrolase-1 transgenic mice are not protected from ischemic stroke. |
| title_sort | dimethylarginine dimethylaminohydrolase 1 transgenic mice are not protected from ischemic stroke |
| url | http://europepmc.org/articles/PMC2753663?pdf=render |
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