Navegando por Palavras-chave "Argininosuccinate synthase"

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    A diversidade estrutural de peptídeos potenciadores da bradicinina da Bothrops jararaca (Bj-BPPs) proporciona ações sinérgicas no sistema cardiovascular
    (Universidade Federal de São Paulo (UNIFESP), 2010-03-31) Morais, Kátia Luciano Pereira [UNIFESP]; Camargo, Antonio Carlos Martins de [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    Our laboratory has shown that one gene codes for the protein precursor that yields the natriuretic peptide type C (CNP) after having been processed, along with a variety of proline-rich peptides, known as bradykinin-potentiating peptides or BPPs. Showing little differences, this precursor is expressed in the venom gland and the neuroendocrine region of the Bothrops jararaca brain. All processing products have in common that they act on the cardiovascular system, lowering arterial blood pressure and heart frequency. This intriguing fact led us to question whether the different peptides display similar mechanisms of action. Surprisingly, the present study showed that the answer is negative, although we cannot, at the present time, explain in full detail how each peptide acts in the complex mechanism, responsible for vascular tonus and cardiac frequency. Historically, the demonstration that the Bradykinin-Potentiating Peptides from Bothrops jararaca (Bj-BPPs) were natural inhibitors of the angiotensin converting enzyme (ACE) had a wide medical impact. In fact, this inhibition seemed to fully explain the strong anti-hypertensive action of these peptides, therefore being employed as structural models for the development of a site-directed inhibitor, Captopril, a drug used worldwide for the treatment of systemic human arterial hypertension. Recent experimental evidences, however, suggest that the anti-hypertensive activity of the Bj-BPPs is not due exclusively to the inhibition of the ACE. Our group demonstrated that the antihypertensive action of Bj-BPP-10c, for instance, is due to the activation of L-arginine generation, which is essential for NO production, a potent vasodilator. Moreover, it also regulates the arterial baroreflex and intracellular calcium signaling, which contribute to NO production in endothelial and neuronal cells. In the present work we studied the mechanism of action of other Bj-BPPs found in the above mentioned precursor. We showed that the mechanism of action of Bj-BPP-5a involves bradykinin B2 receptor, the muscarinic receptor, subtype M1, and NO production. Bj-BPP-11e probably acts on a membrane receptor, thereby explaining its effects on cardiovascular parameters. The mechanism of action of Bj-BPP-12b might be explained by Bk potentiation and/or by ACE inhibition and Bj- BPP-13a action on by muscarinic receptor subtype M3 and the ASS. Interestingly, Bj-BPP-9a, which was the model molecule for the synthesis of Captopril, seems to act predominantly as a classic ACE inhibitor. Beside the pharmacological interest, our work also revealed, for the first time, that snake toxins also employ the well-known strategy in hormone-peptide generation, that is, they use the processing of a polyprotein to generate peptides which display a synergistic action.
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    Enhancement of the citrulline-nitric oxide cycle in astroglioma cells by the proline-rich peptide-10c from Bothrops jararaca venom
    (Elsevier B.V., 2010-12-06) Oliveira, Eduardo Fontana de [UNIFESP]; Guerreiro, Juliano R.; Silva, Carlos A.; Souza Benedetti, Gabriel Fernando de [UNIFESP]; Lebrun, Ivo; Ulrich, Henning; Lameu, Claudiana; Camargo, Antonio C. M.; Inst Butantan; Universidade Federal de São Paulo (UNIFESP); Universidade de São Paulo (USP); Universidade Federal do ABC (UFABC)
    The biological activity of the proline rich decapeptde 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 angiotensm converting enzyme activity with subsequent ant 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 made (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 (C) 2010 Elsevier B V All rights reserved