Dysregulation of L-arginine metabolism and bioavailability associated to free plasma heme
Severe Plasmodium falciparum malaria is associated with hypoargininemia, which contributes to impaired systemic and pulmonary nitric oxide (NO) production and endothelial dysfunction. Since intravascular hemolysis is an intrinsic feature of severe malaria, we investigated whether and by which mechan...
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th-mahidol.286742018-09-24T15:44:04Z Dysregulation of L-arginine metabolism and bioavailability associated to free plasma heme F. Omodeo-Salè L. Cortelezzi Z. Vommaro D. Scaccabarozzi A. M. Dondorp Universita degli Studi di Milano Mahidol University Churchill Hospital Biochemistry, Genetics and Molecular Biology Severe Plasmodium falciparum malaria is associated with hypoargininemia, which contributes to impaired systemic and pulmonary nitric oxide (NO) production and endothelial dysfunction. Since intravascular hemolysis is an intrinsic feature of severe malaria, we investigated whether and by which mechanisms free heme [Fe(III)-protoporphyrin IX (FP)] might contribute to the dysregulation of L-arginine (L-Arg) metabolism and bioavailability. Carrier systems "y+" [or cationic amino acid transporter (CAT)] and "y+L" transport L-Arg into red blood cells (RBC), where it is hydrolyzed to ornithine and urea by arginase (isoform I) or converted to NO•and citrulline by endothelial nitric oxide synthase (eNOS). Our results show a significant and dose-dependent impairment of L-Arg transport into RBC pretreated with FP, with a strong inhibition of the system carrier y+L. Despite the impaired L-Arg influx, higher amounts of L-Arg-derived urea are produced by RBC preexposed to FP caused by activation of RBC arginase I. This activation appeared not to be mediated by oxidative modifications of the enzyme. We conclude that L-Arg transport across RBC membrane is impaired and arginase-mediated L-Arg consumption enhanced by free heme. This could contribute to reduced NO production in severe malaria. Copyright © 2010 the American Physiological Society. 2018-09-24T08:44:04Z 2018-09-24T08:44:04Z 2010-07-01 Article American Journal of Physiology - Cell Physiology. Vol.299, No.1 (2010) 10.1152/ajpcell.00405.2009 15221563 03636143 2-s2.0-77953786118 https://repository.li.mahidol.ac.th/handle/123456789/28674 Mahidol University SCOPUS https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=77953786118&origin=inward |
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Biochemistry, Genetics and Molecular Biology F. Omodeo-Salè L. Cortelezzi Z. Vommaro D. Scaccabarozzi A. M. Dondorp Dysregulation of L-arginine metabolism and bioavailability associated to free plasma heme |
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Severe Plasmodium falciparum malaria is associated with hypoargininemia, which contributes to impaired systemic and pulmonary nitric oxide (NO) production and endothelial dysfunction. Since intravascular hemolysis is an intrinsic feature of severe malaria, we investigated whether and by which mechanisms free heme [Fe(III)-protoporphyrin IX (FP)] might contribute to the dysregulation of L-arginine (L-Arg) metabolism and bioavailability. Carrier systems "y+" [or cationic amino acid transporter (CAT)] and "y+L" transport L-Arg into red blood cells (RBC), where it is hydrolyzed to ornithine and urea by arginase (isoform I) or converted to NO•and citrulline by endothelial nitric oxide synthase (eNOS). Our results show a significant and dose-dependent impairment of L-Arg transport into RBC pretreated with FP, with a strong inhibition of the system carrier y+L. Despite the impaired L-Arg influx, higher amounts of L-Arg-derived urea are produced by RBC preexposed to FP caused by activation of RBC arginase I. This activation appeared not to be mediated by oxidative modifications of the enzyme. We conclude that L-Arg transport across RBC membrane is impaired and arginase-mediated L-Arg consumption enhanced by free heme. This could contribute to reduced NO production in severe malaria. Copyright © 2010 the American Physiological Society. |
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Universita degli Studi di Milano |
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Universita degli Studi di Milano F. Omodeo-Salè L. Cortelezzi Z. Vommaro D. Scaccabarozzi A. M. Dondorp |
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Article |
author |
F. Omodeo-Salè L. Cortelezzi Z. Vommaro D. Scaccabarozzi A. M. Dondorp |
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F. Omodeo-Salè |
title |
Dysregulation of L-arginine metabolism and bioavailability associated to free plasma heme |
title_short |
Dysregulation of L-arginine metabolism and bioavailability associated to free plasma heme |
title_full |
Dysregulation of L-arginine metabolism and bioavailability associated to free plasma heme |
title_fullStr |
Dysregulation of L-arginine metabolism and bioavailability associated to free plasma heme |
title_full_unstemmed |
Dysregulation of L-arginine metabolism and bioavailability associated to free plasma heme |
title_sort |
dysregulation of l-arginine metabolism and bioavailability associated to free plasma heme |
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2018 |
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https://repository.li.mahidol.ac.th/handle/123456789/28674 |
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1763490149121916928 |