Novel ocellatin peptides mitigate LPS-induced ROS formation and NF-kB activation in microglia and hippocampal neurons

Autor: Joilson Ramos-Jesus, Jand Venes R. Medeiros, André Luis Fernandes Lopes, Marcelo P. Bemquerer, Guilherme Antônio Lopes de Oliveira, Renato Socodato, Nayara A. Sousa, Luan Kelves Miranda de Souza, Eder Alves Barbosa, Thiago S.L. Araújo, Camila C. Portugal, Kerolayne M. Nogueira, Bruno Iles, Peter Eaton, Alexandra Plácido, Andrea Lobo, Alyne Rodrigues de Araújo, João B. Relvas, Yuri D. M. Campelo, José Roberto S. A. Leite, Ana Patrícia de Oliveira, Constança Pais do Amaral
Přispěvatelé: Repositório da Universidade de Lisboa, NAYARA A. SOUSA, UNIVERSIDADE FEDERAL DO DELTA DO PARNAÍBA, GUILHERME A. L. OLIVEIRA, UNIVERSIDADE FEDERAL DO DELTA DO PARNAÍBA, ANA PATRÍCIA DE OLIVEIRA, UNIVERSIDADE FEDERAL DO DELTA DO PARNAÍBA, ANDRÉ LUÍS F. LOPES, UNIVERSIDADE FEDERAL DO DELTA DO PARNAÍBA, BRUNO ILES, UNIVERSIDADE FEDERAL DO DELTA DO PARNAÍBA, KEROLAYNE M. NOGUEIRA, UNIVERSIDADE FEDERAL DO DELTA DO PARNAÍBA, THIAGO S. L. ARAÚJO, UNIVERSIDADE FEDERAL DO DELTA DO PARNAÍBA, LUAN K. M. SOUZA, UNIVERSIDADE FEDERAL DO DELTA DO PARNAÍBA, ALYNE R. ARAÚJO, UFPI, JOILSON RAMOS-JESUS, UFPI, ALEXANDRA PLÁCIDO, FACULDADE DE CIENCIAS DA UNIVERSIDADE DO PORTO, PORTUGAL, CONSTANÇA AMARAL, UNIVERSIDADE DE LISBOA, PORTUGAL, YURI D. M. CAMPELO, FAHESP/IESVAP/NRE, EDER ALVES BARBOSA, UNB, CAMILA C. PORTUGAL, FACULDADE DE CIENCIAS DA UNIVERSIDADE DO PORTO, PORTUGAL, RENATO SOCODATO, FACULDADE DE CIENCIAS DA UNIVERSIDADE DO PORTO, PORTUGAL, ANDREA LOBO, FACULDADE DE CIENCIAS DA UNIVERSIDADE DO PORTO, PORTUGAL, JOAO RELVAS, FACULDADE DE CIENCIAS DA UNIVERSIDADE DO PORTO, PORTUGAL, MARCELO PORTO BEMQUERER, Cenargen, PETER EATON, FACULDADE DE CIENCIAS DA UNIVERSIDADE DO PORTO, PORTUGAL, JOSÉ ROBERTO S. A. LEITE, UNB, JAND VENES R. MEDEIROS, UNIVERSIDADE FEDERAL DO DELTA DO PARNAÍBA., Instituto de Investigação e Inovação em Saúde
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Lipopolysaccharides
Lipopolysaccharide
lcsh:Medicine
ComputingMilieux_LEGALASPECTSOFCOMPUTING
Hippocampal formation
medicine.disease_cause
Hippocampus / drug effects
Hippocampus
Mice
chemistry.chemical_compound
0302 clinical medicine
Infections / microbiology
lcsh:Science
Anura / metabolism
Neurons
chemistry.chemical_classification
0303 health sciences
Multidisciplinary
biology
Microglia
Neurons / metabolism
Amino Acid Sequence / genetics
NF-kappa B
Antimicrobial Cationic Peptides / metabolism
Malondialdehyde
medicine.anatomical_structure
Hippocampus / metabolism
Nitrites / antagonists & inhibitors
Natural product synthesis
Anura
Antimicrobial Cationic Peptides / pharmacology
Neurons / drug effects
Infections
Cutaneous secretions
Article
Superoxide dismutase
Amphibians
03 medical and health sciences
Nitrites / metabolism
Lipopolysaccharides / toxicity
medicine
Animals
Antimicrobial Cationic Peptides / chemistry
Amino Acid Sequence
Nitrites
030304 developmental biology
Reactive oxygen species
Leptodactylus vastus
lcsh:R
Reactive Oxygen Species / metabolism
Glutathione
Antimicrobial Cationic Peptides / genetics
Microglia / drug effects
Molecular biology
NF-kappa B / genetics
Pharmacodynamics
chemistry
Infections / genetics
biology.protein
lcsh:Q
Infections / drug therapy
Reactive Oxygen Species
Peptides
Infections / chemically induced
030217 neurology & neurosurgery
Oxidative stress
Antimicrobial Cationic Peptides
Zdroj: Repositório Institucional da EMBRAPA (Repository Open Access to Scientific Information from EMBRAPA-Alice)
Empresa Brasileira de Pesquisa Agropecuária (Embrapa)
instacron:EMBRAPA
Scientific Reports, Vol 10, Iss 1, Pp 1-16 (2020)
Scientific Reports
Repositório Científico de Acesso Aberto de Portugal
Repositório Científico de Acesso Aberto de Portugal (RCAAP)
instacron:RCAAP
Popis: © The Author(s) 2020. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Cre-ative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not per-mitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Cutaneous secretions of amphibians have bioactive compounds, such as peptides, with potential for biotechnological applications. Therefore, this study aimed to determine the primary structure and investigate peptides obtained from the cutaneous secretions of the amphibian, Leptodactylus vastus, as a source of bioactive molecules. The peptides obtained possessed the amino acid sequences, GVVDILKGAAKDLAGH and GVVDILKGAAKDLAGHLASKV, with monoisotopic masses of [M + H]± = 1563.8 Da and [M + H]± = 2062.4 Da, respectively. The molecules were characterized as peptides of the class of ocellatins and were named as Ocellatin-K1(1-16) and Ocellatin-K1(1-21). Functional analysis revealed that Ocellatin-K1(1-16) and Ocellatin-K1(1-21) showed weak antibacterial activity. However, treatment of mice with these ocellatins reduced the nitrite and malondialdehyde content. Moreover, superoxide dismutase enzymatic activity and glutathione concentration were increased in the hippocampus of mice. In addition, Ocellatin-K1(1-16) and Ocellatin-K1(1-21) were effective in impairing lipopolysaccharide (LPS)-induced reactive oxygen species (ROS) formation and NF-kB activation in living microglia. We incubated hippocampal neurons with microglial conditioned media treated with LPS and LPS in the presence of Ocellatin-K1(1-16) and Ocellatin-K1(1-21) and observed that both peptides reduced the oxidative stress in hippocampal neurons. Furthermore, these ocellatins demonstrated low cytotoxicity towards erythrocytes. These functional properties suggest possible to neuromodulatory therapeutic applications.
Alexandra Plácido is a recipient of a post-doctoral grant from the project FCT (PTDC/BII-BIO/31158/2017). Renato Socodato and Camila Cabral Portugal hold postdoctoral fellowships from FCT (Refs: SFRH/BPD/91833/2012 and FRH/BPD/91962/2012, respectively). This work was funded through project UID/QUI/50006/2013-POCI/01/0145/FEDER/007265 (LAQV/REQUIMTE) with financial support from FCT/MEC through national funds and co-financed by FEDER, under the Partnership Agreement PT 2020
Databáze: OpenAIRE