Produção Nacional
Revisado por pares
Enhancement of the citrulline–nitric oxide cycle in astroglioma cells by the proline-rich peptide-10c from Bothrops jararaca venom
2010; Elsevier BV; Volume: 1363; Linguagem: Inglês
10.1016/j.brainres.2010.09.067
ISSN1872-6240
AutoresLeandro G. Oliveira, Juliano R. Guerreiro, Carlos Alberto-Silva, Gabriel Benedetti, Ivo Lebrun, Henning Ulrich, Claudiana Lameu, Antônio Carlos Martins de Camargo,
Tópico(s)Ion channel regulation and function
ResumoThe 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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