Imperial College London
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Dr Aubrey Cunnington

Faculty of Medicine, Department of Infectious Disease

Professor of Paediatric Infectious Disease
 
 
 
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Contact

 

+44 (0)20 7594 3695a.cunnington

 
 
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Location

 

244Norfolk PlaceSt Mary's Campus

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Summary

 

Publications

Citation

BibTex format

@article{Chertow:2015:10.1371/journal.ppat.1005119,
author = {Chertow, JH and Alkaitis, MS and Nardone, G and Ikeda, AK and Cunnington, AJ and Okebe, J and Ebonyi, AO and Njie, M and Correa, S and Jayasooriya, S and Casals-Pascual, C and Billker, O and Conway, DJ and Walther, M and Ackerman, H},
doi = {10.1371/journal.ppat.1005119},
journal = {PLOS Pathogens},
title = {Plasmodium Infection Is Associated with Impaired Hepatic Dimethylarginine Dimethylaminohydrolase Activity and Disruption of Nitric Oxide Synthase Inhibitor/Substrate Homeostasis.},
url = {http://dx.doi.org/10.1371/journal.ppat.1005119},
volume = {11},
year = {2015}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Inhibition of nitric oxide (NO) signaling may contribute to pathological activation of the vascular endothelium during severe malaria infection. Dimethylarginine dimethylaminohydrolase (DDAH) regulates endothelial NO synthesis by maintaining homeostasis between asymmetric dimethylarginine (ADMA), an endogenous NO synthase (NOS) inhibitor, and arginine, the NOS substrate. We carried out a community-based case-control study of Gambian children to determine whether ADMA and arginine homeostasis is disrupted during severe or uncomplicated malaria infections. Circulating plasma levels of ADMA and arginine were determined at initial presentation and 28 days later. Plasma ADMA/arginine ratios were elevated in children with acute severe malaria compared to 28-day follow-up values and compared to children with uncomplicated malaria or healthy children (p<0.0001 for each comparison). To test the hypothesis that DDAH1 is inactivated during Plasmodium infection, we examined DDAH1 in a mouse model of severe malaria. Plasmodium berghei ANKA infection inactivated hepatic DDAH1 via a post-transcriptional mechanism as evidenced by stable mRNA transcript number, decreased DDAH1 protein concentration, decreased enzyme activity, elevated tissue ADMA, elevated ADMA/arginine ratio in plasma, and decreased whole blood nitrite concentration. Loss of hepatic DDAH1 activity and disruption of ADMA/arginine homeostasis may contribute to severe malaria pathogenesis by inhibiting NO synthesis.
AU  - Chertow,JH
AU  - Alkaitis,MS
AU  - Nardone,G
AU  - Ikeda,AK
AU  - Cunnington,AJ
AU  - Okebe,J
AU  - Ebonyi,AO
AU  - Njie,M
AU  - Correa,S
AU  - Jayasooriya,S
AU  - Casals-Pascual,C
AU  - Billker,O
AU  - Conway,DJ
AU  - Walther,M
AU  - Ackerman,H
DO  - 10.1371/journal.ppat.1005119
PY  - 2015///
SN  - 1553-7366
TI  - Plasmodium Infection Is Associated with Impaired Hepatic Dimethylarginine Dimethylaminohydrolase Activity and Disruption of Nitric Oxide Synthase Inhibitor/Substrate Homeostasis.
T2  - PLOS Pathogens
UR  - http://dx.doi.org/10.1371/journal.ppat.1005119
UR  - http://hdl.handle.net/10044/1/26749
VL  - 11
ER  -
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