1. Novel ocellatin peptides mitigate LPS-induced ROS formation and NF-kB activation in microglia and hippocampal neurons
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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, 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., and Instituto de Investigação e Inovação em Saúde
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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 - Abstract
© 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
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- 2020