Increased cationic amino acid flux through a newly expressed transporter in cells overproducing nitric oxide from patients with septic shock.

Increased production of nitric oxide (NO) is thought to be a factor in the pathogenesis of many human diseases - among them the hypotension that often accompanies sepsis. The supply of the cationic amino acid arginine is known to be rate-limiting for NO production. We hypothesized that cationic amin...

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Autores principales: Reade, M, Clark, M, Young, J, Boyd, C
Formato: Journal article
Lenguaje:English
Publicado: 2002
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author Reade, M
Clark, M
Young, J
Boyd, C
author_facet Reade, M
Clark, M
Young, J
Boyd, C
author_sort Reade, M
collection OXFORD
description Increased production of nitric oxide (NO) is thought to be a factor in the pathogenesis of many human diseases - among them the hypotension that often accompanies sepsis. The supply of the cationic amino acid arginine is known to be rate-limiting for NO production. We hypothesized that cationic amino acid transport might be increased in cells producing excess NO from patients with septic shock. Peripheral blood mononuclear cells were isolated from patients with sepsis and from healthy control subjects. The rates of both NO production and cationic amino acid uptake were increased in cells from patients with septic shock. The increased transport was due almost entirely to an increase in the activity of one transporter, subtype y+. The activity of the other major cationic amino acid transporter (y+L) was unchanged. The expression of CAT2 mRNA, which encodes a y+ transporter protein, was also increased in these cells. We suggest that CAT2 might be a therapeutic target to prevent excess NO production in sepsis and possibly other human disease states, while leaving basal production unchanged.
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spelling oxford-uuid:e769d718-00ce-40b6-8478-5f4cef9f31b52022-03-27T10:38:29ZIncreased cationic amino acid flux through a newly expressed transporter in cells overproducing nitric oxide from patients with septic shock.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:e769d718-00ce-40b6-8478-5f4cef9f31b5EnglishSymplectic Elements at Oxford2002Reade, MClark, MYoung, JBoyd, CIncreased production of nitric oxide (NO) is thought to be a factor in the pathogenesis of many human diseases - among them the hypotension that often accompanies sepsis. The supply of the cationic amino acid arginine is known to be rate-limiting for NO production. We hypothesized that cationic amino acid transport might be increased in cells producing excess NO from patients with septic shock. Peripheral blood mononuclear cells were isolated from patients with sepsis and from healthy control subjects. The rates of both NO production and cationic amino acid uptake were increased in cells from patients with septic shock. The increased transport was due almost entirely to an increase in the activity of one transporter, subtype y+. The activity of the other major cationic amino acid transporter (y+L) was unchanged. The expression of CAT2 mRNA, which encodes a y+ transporter protein, was also increased in these cells. We suggest that CAT2 might be a therapeutic target to prevent excess NO production in sepsis and possibly other human disease states, while leaving basal production unchanged.
spellingShingle Reade, M
Clark, M
Young, J
Boyd, C
Increased cationic amino acid flux through a newly expressed transporter in cells overproducing nitric oxide from patients with septic shock.
title Increased cationic amino acid flux through a newly expressed transporter in cells overproducing nitric oxide from patients with septic shock.
title_full Increased cationic amino acid flux through a newly expressed transporter in cells overproducing nitric oxide from patients with septic shock.
title_fullStr Increased cationic amino acid flux through a newly expressed transporter in cells overproducing nitric oxide from patients with septic shock.
title_full_unstemmed Increased cationic amino acid flux through a newly expressed transporter in cells overproducing nitric oxide from patients with septic shock.
title_short Increased cationic amino acid flux through a newly expressed transporter in cells overproducing nitric oxide from patients with septic shock.
title_sort increased cationic amino acid flux through a newly expressed transporter in cells overproducing nitric oxide from patients with septic shock
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AT youngj increasedcationicaminoacidfluxthroughanewlyexpressedtransporterincellsoverproducingnitricoxidefrompatientswithsepticshock
AT boydc increasedcationicaminoacidfluxthroughanewlyexpressedtransporterincellsoverproducingnitricoxidefrompatientswithsepticshock