Novel Ocellatin Peptides Mitigate LPS-induced ROS Formation and NF-kB Activation in Microglia and Hippocampal Neurons
Nayara Alves de Sousa, Guilherme Antônio Lopes de Oliveira, Ana Patrícia de Oliveira, André Luís Fernandes Lopes, Bruno Iles, Kerolayne de Melo Nogueira, Thiago S.L. Araújo, Luan Kelves Miranda de Souza, Alyne Rodrigues de Araújo, Joilson Ramos‐Jesus, Alexandra Plácido, Constança Pais do Amaral, Yuri Dias Macêdo Campelo, Éder Alves Barbosa, Camila C. Portugal, Renato Socodato, Andrea Lobo, João B. Relvas, Marcelo P. Bemquerer, Peter Eaton, J. R. Leite, Jand Venes Rolim Medeiros
Abstract
Abstract 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.