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

Abstract

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.

Avathrin: a novel thrombin inhibitor derived from a multicopy precursor in the salivary glands of the ixodid tick,Amblyomma variegatum

“…Thus, ticks appear to synthesize larger precursors containing multiple variants of thrombin inhibitors. Similar strategies for producing multiple variants are well known (e.g., bradykinin-potentiating peptide precursors in viperid snake venoms) (42,43). Because adult Amblyomma species feed on their hosts for as long as 12 d (44), using such a strategy could be advantageous to the tick in offering potent inhibition of coagulation while minimizing chances of host rejection, cost of protein synthesis, and perhaps tunable expression profiles, depending on feeding stages.…”

Studies about Snake Peptides: a Review about Brazilian Contribution

“…The species of this genus are distributed throughout all regions of Brazil and, due to this wide distribution, encounters with humans are common, making these snakes responsible for almost 90% of snakebites in the country [81]. The B. jararaca species has been studied from 1975 to the present day in terms of bradykinin-potentiating peptides [20,41,[82][83][84][85][86]. These peptides are antihypertensive molecules that inhibit the degradation of a hypotensive peptide and the formation of a vasoconstrictor peptide [87].…”

Ten years of research on bioactive peptides in Brazil: a scientometric analysis

“…Aguilar et al (2020); Alberto-Silva et al (2020);Amorim et al (2018);Amorim et al (2019);Baptista et al (2018);Baptista et al (2020a);Baptista et al (2020b);Barati et al (2020);Bassan et al (2016);Bezerra et al (2019);Brandelli et al (2015);Callegaro et al (2018);Campeiro et al (2015);Cavalheiro et al (2020);Corrêa et al (2011);Corrêa et al (2014);Coutinho-Neto et al (2013); Da; De Oliveira et al (2020); De Oliveira et al (2021); Fontenele et al (2017); Freitas et al (2020); Fucase et al (2017); Galli et al (2019); Latorres et al (2021); Meira et al (2012); Mezzomo et al (2021); Michelon et al (2021); Miltenburg et al (2021); Nascimento et al (2021b); Oliveira Filho et al (2021); Piotrowicz et al (2020); Pucca et al (2016); Ribeiro et al (2021); Silva et al (2019a); Vanzolini et al (2018); Yesmine et al (2017) Anti-inflammatory Inhibition of pro-inflammatory substances and cells Brand et al (2019); Grancieri et al (2019); Henaux et al (2021); Lima et al (2019); Michelon et al (2021); Rosa et al (2012); Vernaza et al (2012) Antinociceptive/ antalgic Inhibition of sensitivity to painful stimuli Galli et al (2019); Oliveira et al (2019a); Ribeiro et al (2013) Antioxidant Reduction of free radical oxidation and lipid peroxidation Aguilar et al (2020); Barati et al (2020); Barbosa et al (2018); Bassan et al (2016); Bertolini et al (2021); Bezerra et al (2013); Bezerra et al (2020); Brandelli et al (2015); Callegaro et al (2018); Corrêa et al (2011); Corrêa et al (2014); Corrêa et al (2019); Cruz et al (2020); Daroit et al (2012); Delgado-García et al (2019); Duarte Neto et al (2017); Fontenele et al (2017); Fontoura et al (2019); Graziani et al (2021); Latorres et al (2018); Latorres et al (2021); Lima et al (2015); Lima et al (2018); Mandal et al (2014); Marson et al (2020); Matos et al (2021); Meira et al (2012); Michelon et al (2021); Montalvo et al (2019); Moura et al (2016); Nascimento et al (2021a); Nascimento et al (2021b); Hamin Neto et al (2019); Ohara et al (2020); Oliveira Filho et al (2021); Oliveira et al (2017); Oliveira et al (2019b); Pazinatto et al (2013); Pereira et al (2019); Piotrowicz et al (2020); Plácido et al (2020); Quadros et al (2019); Ribeiro et al (2021); Romani et al (2020); Sbroggio et al (2016); Silva et al (2012); Silva et al (2019a); Silva et al (2019b); Silva et al (2021); Sousa et al (2020); Venancio et al (2013); Vernaza et al (2012); Vogel et al (2021); Yekta et al (2020); Zanutto-Elgui et al (2019) Antiparasitic Broad-spectrum endo-and ectoparasiticide Boelter et al (2020); Mendes et al (2019); Mongui et al (2015); Rádis-Baptista et al (2020); Traoré et al (2013) Antiproliferative Inhibition of proliferation of non-cancerous cells and benign prostatic hyperplasia Santana et al (2020) Antisclerotic Inhibition of...…”