Proline rich-oligopeptides: Diverse mechanisms for antihypertensive action

Morais, Katia L.P.; Ianzer, Danielle; Miranda, José Rodolfo R.; Melo, Robson L.; Guerreiro, Juliano R.; Santos, Robson A.S.; Ulrich, Henning; Lameu, Claudiana

doi:10.1016/j.peptides.2013.07.016

Cited by 32 publications

(32 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Proline-rich oligopeptides (PROs) represent a class of peptides firstly isolated from the Bothrops jararaca venom, which present proline residues at their C-terminal portions and inhibitory activity of the angiotensin-I converting enzyme (ACE) as well as the potentiation of bradykinin effects (Camargo et al 2012;Morais et al 2013). Furthermore, secretions and venoms from other animals, such as amphibians and scorpions have also been described as a potential source of PROs with potential applications (Conceição et al 2007;Verano-Braga et al 2008).…”

Section: Introductionmentioning

confidence: 99%

In Silico, In Vitro and In Vivo Toxicological Assessment of BPP-BrachyNH2, A Vasoactive Proline-Rich Oligopeptide from Brachycephalus ephippium

Arcanjo

Mafud

Vasconcelos

et al. 2016

Int J Pept Res Ther

View full text Add to dashboard Cite

BPP-BrachyNH 2 is a proline-rich oligopeptide (PRO) firstly identified in skin secretion of the frog Brachycephalus ephippium, which possess in vitro inhibitory activity of angiotensin-I converting enzyme (ACE) and endothelium-dependent vasorelaxant activity. Considering its potential application in the treatment of cardiovascular diseases, the present work assessed the toxicological profile of the BPP-BrachyNH 2 . The in silico toxicity prediction was performed from the best model obtained through the optimization of the FASTA query peptide. This prediction study revealed that BPP-BrachyNH 2 induced high predicted LD 50 values for both humans and rats, and then is well-tolerated in the recommended range. The MTT assay was applied for the in vitro cytotoxic evaluation in murine macrophages. In this assay, a decrease of cell viability was not observed. The in vivo acute toxicological study was performed after the intraperitoneal administration of BPP-BrachyNH 2 at doses of 5 and 50 mg/kg. After intraperitoneal administration, no death, alterations in behavioral parameters or weight gain curve was observed, as well as none in the serum biochemical parameters, and gross pathological and histopathological analyses. These observations demonstrates an acceptable safety profile for BPP-BrachyNH 2 , leading towards further studies focused on investigation of pharmacological and therapeutical applications for this peptide.

show abstract

Section: Introductionmentioning

confidence: 99%

In Silico, In Vitro and In Vivo Toxicological Assessment of BPP-BrachyNH2, A Vasoactive Proline-Rich Oligopeptide from Brachycephalus ephippium

Arcanjo

Mafud

Vasconcelos

et al. 2016

Int J Pept Res Ther

View full text Add to dashboard Cite

show abstract

“…The positive control, suramin, had an IC 50 value of 2.5 mg/mL (Table 1). Proline derivatives have been reported to possess antifungal, antiangiotensin-converting enzyme (ACE) (Morais et al, 2013) and antiviral (Zhou et al, 2013) activities. It has been reported that methionineproline anilides can inhibit the protease enzyme of dengue virus NS2B-NS3 (Zhou et al, 2013).…”

Section: Resultsmentioning

confidence: 99%

Anti-HIV-1 integrase effect of compounds fromAglaia andamanicaleaves and molecular docking study with acute toxicity test in mice

Puripattanavong

Tungcharoen

Chaniad

et al. 2015

Pharmaceutical Biology

View full text Add to dashboard Cite

show abstract

“…This difference was not significant as determined by the variation in the maximum peak response for each animal, but it is important to note that, for each animal, the maximum response was observed at different time lapses, i.e. at 5, 10, 15, 20, 25 or 30 min after peptide IV bolus injection ( Figure 6A However, in contrast to the SODa peptide (Table 4, Figure 6C-F) and the ACE inhibitory activity described for the snake BPPs [56], for concentrations up to 120 nmol, the SODb peptide showed no obvious ACE inhibition, evaluated by in vivo potentiation of the BK hypotensive effects in anaesthetized rats (data now shown).…”

Section: The Activity After Peripheral Injection Of Synthetic Soda [Pmentioning

confidence: 96%

“…The employment of several innovative strategies culminated in the production of anti-BPPs antiserum able to recognize a single band corresponding to the BPP precursor protein in the cytosol of the Bothrops jararaca venom gland [56], but which was not able to specifically recognize proteins in any other snake or rat tissue homogenates (data not shown). In the present work, we demonstrate the high specificity of anti-BPPs antiserum raised in mice by several immunization protocols using purified recombinant BPP precursor protein expressed in bacteria, which was shown to be able to recognize a single protein band in the whole cytosol of snake and rat brain, independent of the immunization protocol used.…”

Section: Page 28 Of 54mentioning

confidence: 99%

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

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Proline rich-oligopeptides: Diverse mechanisms for antihypertensive action

Cited by 32 publications

References 37 publications

In Silico, In Vitro and In Vivo Toxicological Assessment of BPP-BrachyNH2, A Vasoactive Proline-Rich Oligopeptide from Brachycephalus ephippium

In Silico, In Vitro and In Vivo Toxicological Assessment of BPP-BrachyNH2, A Vasoactive Proline-Rich Oligopeptide from Brachycephalus ephippium

Anti-HIV-1 integrase effect of compounds fromAglaia andamanicaleaves and molecular docking study with acute toxicity test in mice

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

Contact Info

Product

Resources

About