Neuroprotective effects on microglia and insights into the structure–activity relationship of an antioxidant peptide isolated from Pelophylax perezi

Detalhes bibliográficos
Autor(a) principal: Plácido, Alexandra
Data de Publicação: 2022
Outros Autores: Amaral, Constança do Pais do, Teixeira, Cátia, Nogueira, Ariane, Brango-Vanegas, José, Barbosa, Eder Alves, Moreira, Daniel C., Carvalho, Amandda É. Silva, Silva, Maria da Gloria da, Dias, Jhones do Nascimento, Albuquerque, Patrícia, Saldanha-Araújo, Felipe, Lima, Filipe C. D. A., Batagin-Neto, Augusto [UNESP], Kuckelhaus, Selma, Bessa, Lucinda J., Freitas, Jaime, Dotto Brand, Guilherme, Santos, Nuno C., Relvas, João B., Gomes, Paula, Leite, José Roberto S. A., Eaton, Peter
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UNESP
Texto Completo: http://dx.doi.org/10.1111/jcmm.17292
http://hdl.handle.net/11449/240882
Resumo: Tryptophyllins constitute a heterogeneous group of peptides that are one of the first classes of peptides identified from amphibian’s skin secretions. Here, we report the structural characterization and antioxidant properties of a novel tryptophyllin-like peptide, named PpT-2, isolated from the Iberian green frog Pelophylax perezi. The skin secretion of P. perezi was obtained by electrical stimulation and fractionated using RP-HPLC. De novo peptide sequencing was conducted using MALDI MS/MS. The primary structure of PpT-2 (FPWLLS-NH2) was confirmed by Edman degradation and subsequently investigated using in silico tools. PpT-2 shared physicochemical properties with other well-known antioxidants. To test PpT-2 for antioxidant activity in vitro, the peptide was synthesized by solid phase and assessed in the chemical-based ABTS and DPPH scavenging assays. Then, a flow cytometry experiment was conducted to assess PpT-2 antioxidant activity in oxidatively challenged murine microglial cells. As predicted by the in silico analyses, PpT-2 scavenged free radicals in vitro and suppressed the generation of reactive species in PMA-stimulated BV-2 microglia cells. We further explored possible bioactivities of PpT-2 against prostate cancer cells and bacteria, against which the peptide exerted a moderate antiproliferative effect and negligible antimicrobial activity. The biocompatibility of PpT-2 was evaluated in cytotoxicity assays and in vivo toxicity with Galleria mellonella. No toxicity was detected in cells treated with up to 512 µg/ml and in G. mellonella treated with up to 40 mg/kg PpT-2. This novel peptide, PpT-2, stands as a promising peptide with potential therapeutic and biotechnological applications, mainly for the treatment/prevention of neurodegenerative disorders.
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spelling Neuroprotective effects on microglia and insights into the structure–activity relationship of an antioxidant peptide isolated from Pelophylax pereziAmphibiaantioxidantbioactive peptideneuroprotectionPelophylax perezitryptophyllinTryptophyllins constitute a heterogeneous group of peptides that are one of the first classes of peptides identified from amphibian’s skin secretions. Here, we report the structural characterization and antioxidant properties of a novel tryptophyllin-like peptide, named PpT-2, isolated from the Iberian green frog Pelophylax perezi. The skin secretion of P. perezi was obtained by electrical stimulation and fractionated using RP-HPLC. De novo peptide sequencing was conducted using MALDI MS/MS. The primary structure of PpT-2 (FPWLLS-NH2) was confirmed by Edman degradation and subsequently investigated using in silico tools. PpT-2 shared physicochemical properties with other well-known antioxidants. To test PpT-2 for antioxidant activity in vitro, the peptide was synthesized by solid phase and assessed in the chemical-based ABTS and DPPH scavenging assays. Then, a flow cytometry experiment was conducted to assess PpT-2 antioxidant activity in oxidatively challenged murine microglial cells. As predicted by the in silico analyses, PpT-2 scavenged free radicals in vitro and suppressed the generation of reactive species in PMA-stimulated BV-2 microglia cells. We further explored possible bioactivities of PpT-2 against prostate cancer cells and bacteria, against which the peptide exerted a moderate antiproliferative effect and negligible antimicrobial activity. The biocompatibility of PpT-2 was evaluated in cytotoxicity assays and in vivo toxicity with Galleria mellonella. No toxicity was detected in cells treated with up to 512 µg/ml and in G. mellonella treated with up to 40 mg/kg PpT-2. This novel peptide, PpT-2, stands as a promising peptide with potential therapeutic and biotechnological applications, mainly for the treatment/prevention of neurodegenerative disorders.Department of Chemistry and Biochemistry LAQV/REQUIMTE Faculty of Sciences University of PortoInstituto de Medicina Molecular Faculdade de Medicina Universidade de LisboaCenter for Research in Applied Morphology and Immunology (NuPMIA) University of BrasiliaLaboratory of Synthesis and Analysis of Biomolecules (LSAB) Institute of Chemistry (IQ) University of BrasiliaLaboratory of Hematology and Stem Cells Faculty of Health Sciences University of BrasiliaDepartment of Cell Biology Institute of Biological Sciences University of BrasíliaBiomedicine Course Federal University of Delta do Parnaíba (UFDPar)Faculty of Ceilândia University of BrasiliaFederal Institute of Education Science and Technology of São PauloSão Paulo State University (UNESP) Campus of Itapeva, SPEgas Moniz Interdisciplinary Research Center (CiiEM) Egas Moniz - Cooperative for Higher Education CRLInstitute for Research and Innovation in Health (i3S) National Institute of Biomedical Engineering (INEB) University of PortoInstitute for Research and Innovation in Health (i3S) Institute for Molecular and Cell Biology (IBMC) University of PortoThe Bridge School of Chemistry Joseph Banks Laboratories University of LincolnSão Paulo State University (UNESP) Campus of Itapeva, SPUniversity of PortoUniversidade de LisboaUniversity of BrasiliaUniversity of BrasíliaFederal University of Delta do Parnaíba (UFDPar)Science and Technology of São PauloUniversidade Estadual Paulista (UNESP)CRLUniversity of LincolnPlácido, AlexandraAmaral, Constança do Pais doTeixeira, CátiaNogueira, ArianeBrango-Vanegas, JoséBarbosa, Eder AlvesMoreira, Daniel C.Carvalho, Amandda É. SilvaSilva, Maria da Gloria daDias, Jhones do NascimentoAlbuquerque, PatríciaSaldanha-Araújo, FelipeLima, Filipe C. D. A.Batagin-Neto, Augusto [UNESP]Kuckelhaus, SelmaBessa, Lucinda J.Freitas, JaimeDotto Brand, GuilhermeSantos, Nuno C.Relvas, João B.Gomes, PaulaLeite, José Roberto S. A.Eaton, Peter2023-03-01T20:36:54Z2023-03-01T20:36:54Z2022-05-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article2793-2807http://dx.doi.org/10.1111/jcmm.17292Journal of Cellular and Molecular Medicine, v. 26, n. 10, p. 2793-2807, 2022.1582-1838http://hdl.handle.net/11449/24088210.1111/jcmm.172922-s2.0-85128779284Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengJournal of Cellular and Molecular Medicineinfo:eu-repo/semantics/openAccess2023-03-01T20:36:55Zoai:repositorio.unesp.br:11449/240882Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T15:30:14.995578Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false
dc.title.none.fl_str_mv Neuroprotective effects on microglia and insights into the structure–activity relationship of an antioxidant peptide isolated from Pelophylax perezi
title Neuroprotective effects on microglia and insights into the structure–activity relationship of an antioxidant peptide isolated from Pelophylax perezi
spellingShingle Neuroprotective effects on microglia and insights into the structure–activity relationship of an antioxidant peptide isolated from Pelophylax perezi
Plácido, Alexandra
Amphibia
antioxidant
bioactive peptide
neuroprotection
Pelophylax perezi
tryptophyllin
title_short Neuroprotective effects on microglia and insights into the structure–activity relationship of an antioxidant peptide isolated from Pelophylax perezi
title_full Neuroprotective effects on microglia and insights into the structure–activity relationship of an antioxidant peptide isolated from Pelophylax perezi
title_fullStr Neuroprotective effects on microglia and insights into the structure–activity relationship of an antioxidant peptide isolated from Pelophylax perezi
title_full_unstemmed Neuroprotective effects on microglia and insights into the structure–activity relationship of an antioxidant peptide isolated from Pelophylax perezi
title_sort Neuroprotective effects on microglia and insights into the structure–activity relationship of an antioxidant peptide isolated from Pelophylax perezi
author Plácido, Alexandra
author_facet Plácido, Alexandra
Amaral, Constança do Pais do
Teixeira, Cátia
Nogueira, Ariane
Brango-Vanegas, José
Barbosa, Eder Alves
Moreira, Daniel C.
Carvalho, Amandda É. Silva
Silva, Maria da Gloria da
Dias, Jhones do Nascimento
Albuquerque, Patrícia
Saldanha-Araújo, Felipe
Lima, Filipe C. D. A.
Batagin-Neto, Augusto [UNESP]
Kuckelhaus, Selma
Bessa, Lucinda J.
Freitas, Jaime
Dotto Brand, Guilherme
Santos, Nuno C.
Relvas, João B.
Gomes, Paula
Leite, José Roberto S. A.
Eaton, Peter
author_role author
author2 Amaral, Constança do Pais do
Teixeira, Cátia
Nogueira, Ariane
Brango-Vanegas, José
Barbosa, Eder Alves
Moreira, Daniel C.
Carvalho, Amandda É. Silva
Silva, Maria da Gloria da
Dias, Jhones do Nascimento
Albuquerque, Patrícia
Saldanha-Araújo, Felipe
Lima, Filipe C. D. A.
Batagin-Neto, Augusto [UNESP]
Kuckelhaus, Selma
Bessa, Lucinda J.
Freitas, Jaime
Dotto Brand, Guilherme
Santos, Nuno C.
Relvas, João B.
Gomes, Paula
Leite, José Roberto S. A.
Eaton, Peter
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv University of Porto
Universidade de Lisboa
University of Brasilia
University of Brasília
Federal University of Delta do Parnaíba (UFDPar)
Science and Technology of São Paulo
Universidade Estadual Paulista (UNESP)
CRL
University of Lincoln
dc.contributor.author.fl_str_mv Plácido, Alexandra
Amaral, Constança do Pais do
Teixeira, Cátia
Nogueira, Ariane
Brango-Vanegas, José
Barbosa, Eder Alves
Moreira, Daniel C.
Carvalho, Amandda É. Silva
Silva, Maria da Gloria da
Dias, Jhones do Nascimento
Albuquerque, Patrícia
Saldanha-Araújo, Felipe
Lima, Filipe C. D. A.
Batagin-Neto, Augusto [UNESP]
Kuckelhaus, Selma
Bessa, Lucinda J.
Freitas, Jaime
Dotto Brand, Guilherme
Santos, Nuno C.
Relvas, João B.
Gomes, Paula
Leite, José Roberto S. A.
Eaton, Peter
dc.subject.por.fl_str_mv Amphibia
antioxidant
bioactive peptide
neuroprotection
Pelophylax perezi
tryptophyllin
topic Amphibia
antioxidant
bioactive peptide
neuroprotection
Pelophylax perezi
tryptophyllin
description Tryptophyllins constitute a heterogeneous group of peptides that are one of the first classes of peptides identified from amphibian’s skin secretions. Here, we report the structural characterization and antioxidant properties of a novel tryptophyllin-like peptide, named PpT-2, isolated from the Iberian green frog Pelophylax perezi. The skin secretion of P. perezi was obtained by electrical stimulation and fractionated using RP-HPLC. De novo peptide sequencing was conducted using MALDI MS/MS. The primary structure of PpT-2 (FPWLLS-NH2) was confirmed by Edman degradation and subsequently investigated using in silico tools. PpT-2 shared physicochemical properties with other well-known antioxidants. To test PpT-2 for antioxidant activity in vitro, the peptide was synthesized by solid phase and assessed in the chemical-based ABTS and DPPH scavenging assays. Then, a flow cytometry experiment was conducted to assess PpT-2 antioxidant activity in oxidatively challenged murine microglial cells. As predicted by the in silico analyses, PpT-2 scavenged free radicals in vitro and suppressed the generation of reactive species in PMA-stimulated BV-2 microglia cells. We further explored possible bioactivities of PpT-2 against prostate cancer cells and bacteria, against which the peptide exerted a moderate antiproliferative effect and negligible antimicrobial activity. The biocompatibility of PpT-2 was evaluated in cytotoxicity assays and in vivo toxicity with Galleria mellonella. No toxicity was detected in cells treated with up to 512 µg/ml and in G. mellonella treated with up to 40 mg/kg PpT-2. This novel peptide, PpT-2, stands as a promising peptide with potential therapeutic and biotechnological applications, mainly for the treatment/prevention of neurodegenerative disorders.
publishDate 2022
dc.date.none.fl_str_mv 2022-05-01
2023-03-01T20:36:54Z
2023-03-01T20:36:54Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://dx.doi.org/10.1111/jcmm.17292
Journal of Cellular and Molecular Medicine, v. 26, n. 10, p. 2793-2807, 2022.
1582-1838
http://hdl.handle.net/11449/240882
10.1111/jcmm.17292
2-s2.0-85128779284
url http://dx.doi.org/10.1111/jcmm.17292
http://hdl.handle.net/11449/240882
identifier_str_mv Journal of Cellular and Molecular Medicine, v. 26, n. 10, p. 2793-2807, 2022.
1582-1838
10.1111/jcmm.17292
2-s2.0-85128779284
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Journal of Cellular and Molecular Medicine
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 2793-2807
dc.source.none.fl_str_mv Scopus
reponame:Repositório Institucional da UNESP
instname:Universidade Estadual Paulista (UNESP)
instacron:UNESP
instname_str Universidade Estadual Paulista (UNESP)
instacron_str UNESP
institution UNESP
reponame_str Repositório Institucional da UNESP
collection Repositório Institucional da UNESP
repository.name.fl_str_mv Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)
repository.mail.fl_str_mv
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