Insights into cardiovascular effects of proline-rich oligopeptide (Bj-PRO-10c) revealed by structure–activity analyses: dissociation of antihypertensive and bradycardic effects

Paschoal, Juliana F. B.; Yamaguchi, Juliana; Miranda, José Rodolfo R.; Carretero, Gustavo; Melo, Robson L.; Santos, Robson A.S.; Xavier, Carlos Henrique; Schreier, Shirley; Camargo, Antônio Carlos Martins de; Ianzer, Danielle

doi:10.1007/s00726-013-1630-x

Cited by 10 publications

(9 citation statements)

References 34 publications

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“…A significant decrease in mean arterial pressure (MAP) accompanied by a significant decrease in heart rate (HR) was observed for both SODa and SODb, in a similar way as recently described also for the snake BPPs [31,32,36,57,66], but with a slower and long lasting effect for SODb compared to the faster effect of SODa (data not shown). Considering that the rat SOD enzyme has a key role in regulating the BP, acting as an endogenous antioxidant [67], it would be expected that peptide fragments derived from SOD protein sequence could be biologically effective only in conditions suitable for the antioxidant system's triggering.…”

Section: Page 31 Of 54supporting

confidence: 69%

“…Interestingly, infusion of these synthetic SOD peptides into spontaneously hypertensive rats (SHRs) brain showed bradycardic and hypotensive effects in these animals, in similar fashion as already described for several BPPs isolated from snakes [66], suggesting a potential physiological central…”

Section: Page 28 Of 54mentioning

confidence: 71%

“…Moreover, it is of note that despite the recognized and overestimated importance of the canonical PIPP sequence in the C-terminus of the snake BPPs for their biological activity on potentiating the BK effects in isolated smooth muscles [34,35], the recent find of the group showed that the N-terminal variable region plays a more decisive role for the in vivo effects of BPPs in the BP, and a dissociation of antihypertensive and bradycardic effects of snake BPPs [66]. Interestingly, among the various biological functions endowed by PRPs present in many tissues and biological fluids of humans, we highlight the antioxidant properties and the potential therapeutic role of PRPs as a promising source of new peptide based novel drugs [73].…”

Section: Page 31 Of 54mentioning

confidence: 95%

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Identification of snake bradykinin-potentiating peptides (BPPs)-simile sequences in rat brain – Potential BPP-like precursor protein?

Campeiro

Neshich

Sant’Anna

et al. 2015

Biochemical Pharmacology

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Bradykinin-potentiating peptides (BPPs) from the South American pit viper snake venom were the first natural inhibitors of the human angiotensin I-converting enzyme (ACE) described. The pioneer characterization of the BPPs precursor from the snake venom glands by our group showed for the first time the presence of the C-type natriuretic peptide (CNP) in this same viper precursor protein. The confirmation of the BPP/CNP expression in snake brain regions correlated with neuroendocrine functions stimulated us to pursue the physiological correlates of these vasoactive peptides in mammals. Notably, several snake toxins were shown to have endogenous physiological correlates in mammals. In the present work, we expressed in bacteria the BPPs domain of the snake venom gland precursor protein, and this purified recombinant protein was used to raise specific polyclonal anti-BPPs antibodies. The correspondent single protein band immune-recognized in adult rat brain cytosol was isolated by 2D-SDS/PAGE and/or HPLC, before characterization by MS fingerprint analysis, which identified this protein as superoxide dismutase (SOD, EC 1.15.1.1), a classically known enzyme with antioxidant activity and important roles in the blood pressure modulation. In silico analysis showed the exposition of the BPP-like peptide sequences on the surface of the 3D structure of rat SOD. These peptides were chemically synthesized to show the BPP-like biological activities in ex vivo and in vivo pharmacological bioassays. Taken together, our data suggest that SOD protein have the potential to be a source for putative BPP-like bioactive peptides, which once released may contribute to the blood pressure control in mammals.

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Section: Page 31 Of 54supporting

confidence: 69%

Section: Page 28 Of 54mentioning

confidence: 71%

Section: Page 31 Of 54mentioning

confidence: 95%

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Identification of snake bradykinin-potentiating peptides (BPPs)-simile sequences in rat brain – Potential BPP-like precursor protein?

Campeiro

Neshich

Sant’Anna

et al. 2015

Biochemical Pharmacology

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“…Efforts are being made to study the structure function relationship of this type of peptides in detail, and their possible modes of blood pressure lowering or vasodilatation. For example it was shown that the peptide Bj-PRO-10c [ 19 ] inhibits ACE, however argininosuccinate synthetase, present in the kidney cytosol is its primary target [ 15 , 19 – 21 ].…”

Section: Introductionmentioning

confidence: 99%

Isolation and characterization of Bradykinin potentiating peptides from Agkistrodon bilineatus venom

et al. 2016

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BackgroundSnake venom is a source of many pharmacologically important molecules. Agkistrodon bilineatus commonly known as Cantil, is spread over Central America particularly in Mexico and Costa Rica. From the venom of Agkistrodon bilineatus we have isolated and characterised six hypotensive peptides, and two bradykinin inhibitor peptides. The IC-50 value of four synthesized peptides was studied, towards angiotensin converting enzyme, in order to study the structure-function relationship of these peptides.ResultsThe purification of the peptides was carried out by size exclusion chromatography, followed by reverse phase chromatography. Sequences of all peptides were determined applying MALDI-TOF/TOF mass spectrometry. These hypotensive peptides bear homology to bradykinin potentiating peptides and venom vasodilator peptide. The peptide with m/z 1355.53 (M + H)+1, and the corresponding sequence ZQWAQGRAPHPP, we identified for the first time. A precursor protein containing a fragment of this peptide was reported at genome level, (Uniprot ID P68515), in Bothrops insularis venom gland. These proline rich hypotensive peptides or bradykinin potentiating peptides are usually present in the venom of Crotalinae, and exhibit specificity in binding to the C domain of somatic angiotensin converting enzyme. Four of these hypotensive peptides, were selected and synthesized to obtain the required quantity to study their IC50 values in complex with the angiotensin converting enzyme. The peptide with the sequence ZLWPRPQIPP displayed the lowest IC50 value of 0.64 μM. The IC50 value of the peptide ZQWAQGRAPHPP was 3.63 μM.ConclusionThe canonical snake venom BPPs classically display the IPP motif at the C-terminus. Our data suggest that the replacement of the highly conserved hydrophobic isoleucine by histidine does not affect the inhibitory activity, indicating that isoleucine is not mandatory to inhibit the angiotensin converting enzyme. The evaluation of IC 50 values show that the peptide with basic pI value exhibits a lower IC 50 value.

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“…A variação na distância entre Phe16-19 F e Leu19-13 C de 10,8 Å em solução, para 5,0 e 6,4 Å em DMPC e PC:SM, respectivamente, evidencia a estruturação do peptídeo nessa região (Lam et al, 2010). As distâncias entre Phe16-19 F e DMPC- 31 visto por outras técnicas, mostram um aumento do conteúdo helicoidal do peptídeo.…”

Section: Estudos Do Mecanismo De Ação Das Actinoporinas Por Meio De Punclassified

Estudos biofísicos e de atividade de peptídeos correspondentes ao N-terminal das toxinas esticolisinais I e II - contribuição para a elucidação do mecanismo de ação

Carretero¹

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Primeiramente à minha família. Aos meus pais, Manoel e Vera, e aos meus irmãos Rafael e Heloísa. Aos meus avós, Sebastião e Augusta, e Carlos e Mari, e à minha bisavó Olívia. E aos meus padrinhos. Aos membros do laboratório companheiros dessa jornada, em especial à Denise e ao José Carlos, com quem pude dividir grande parte das experiências vivenciadas ao longo do desenvolvimento do projeto. À Alessandra. Também à Joana pela oportunidade de fazer parte do projeto, e ao Fábio Dyszy pela ajuda com os primeiros passos no laboratório. Aos cubanos parceiros de projeto Professsores Carlos Alvarez, Marilyn, Fabiola, Aisel e Uris, à Yadira e à Aracelys. Obrigado pela oportunidade e pela satisfação de dividir o projeto por todos esses anos, pelas conversas acerca ou não do projeto e por todo intercâmbio cultural que pude vivenciar.

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Insights into cardiovascular effects of proline-rich oligopeptide (Bj-PRO-10c) revealed by structure–activity analyses: dissociation of antihypertensive and bradycardic effects

Cited by 10 publications

References 34 publications

Identification of snake bradykinin-potentiating peptides (BPPs)-simile sequences in rat brain – Potential BPP-like precursor protein?

Identification of snake bradykinin-potentiating peptides (BPPs)-simile sequences in rat brain – Potential BPP-like precursor protein?

Isolation and characterization of Bradykinin potentiating peptides from Agkistrodon bilineatus venom

Estudos biofísicos e de atividade de peptídeos correspondentes ao N-terminal das toxinas esticolisinais I e II - contribuição para a elucidação do mecanismo de ação

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