| Enhancement of the citrulline-nitric oxide cycle in astroglioma cells by the proline-rich peptide-10c from Bothrops jararaca venom. | |
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MedLine Citation:
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PMID: 20875803 Owner: NLM Status: In-Process |
Abstract/OtherAbstract:
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The biological activity of the proline-rich decapeptide Bj-PRO-10c, a processing product of the C-type natriuretic peptide precursor protein, expressed in the brain and the venom gland of the pit viper Bothrops jararaca, was originally attributed to the inhibition of the somatic angiotensin-converting enzyme activity with subsequent anti-hypertensive effect. However, recent results suggest broader biological activity may also be involved in the cardiovascular effects of this peptide. Here we show that Bj-PRO-10c enhances and sustains the generation of nitric oxide (NO) by regulating argininosuccinate synthase activity and thereby velocity of the citrulline-NO cycle. Bj-PRO-10c-mediated effects not restricted to the cardiovascular system, since NO production was also induced in cells of astroglial origin. Bj-PRO-10c was internalized by C6 astroglioma cells where it induces NO production and upregulation of the citrulline-NO cycle cells in a dose-dependent fashion. In view of that, astroglial cells function as L-arginine pool for NO production in neighboring neurons, we suggest a regulatory function for Bj-PRO-10c on the metabolism of this gaseous neurotransmitter in the CNS. Moreover, proliferation of astroglial cells was reduced in the presence of Bj-PRO-10c; however, cell death was not induced. Since NO donors have been studied for the treatment of solid cancers, Bj-PRO-10c may serve as structural model for developing drugs to improve the effects of cancer therapy based on the peptide's ability to augment NO production. |
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Authors:
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Eduardo Fontana de Oliveira; Juliano R Guerreiro; Carlos A Silva; Gabriel Fernando de Souza Benedetti; Ivo Lebrun; Henning Ulrich; Claudiana Lameu; Antonio C M Camargo |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-09-25 |
Journal Detail:
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Title: Brain research Volume: 1363 ISSN: 1872-6240 ISO Abbreviation: Brain Res. Publication Date: 2010 Dec |
Date Detail:
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Created Date: 2010-11-09 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0045503 Medline TA: Brain Res Country: Netherlands |
Other Details:
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Languages: eng Pagination: 11-9 Citation Subset: IM |
Copyright Information:
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Copyright © 2010 Elsevier B.V. All rights reserved. |
Affiliation:
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Center for Applied Toxinology - CAT-CEPID, Instituto Butantan, SP, Brazil. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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