Biochemical characterization and assessment of leishmanicidal effects of a new L-amino acid oxidase from Crotalus durissus collilineatus snake venom (CollinLA AO-I).

Autor: de Freitas V; Laboratory of Biochemistry and Animal Toxins, Institute of Biotechnology, Federal University of Uberlândia - UFU, Uberlândia, MG, Brazil., Costa TR; Laboratory of Biochemistry and Animal Toxins, Institute of Biotechnology, Federal University of Uberlândia - UFU, Uberlândia, MG, Brazil., Nogueira AR; Laboratory of Biochemistry and Animal Toxins, Institute of Biotechnology, Federal University of Uberlândia - UFU, Uberlândia, MG, Brazil., Polloni L; Laboratory of Biochemistry and Animal Toxins, Institute of Biotechnology, Federal University of Uberlândia - UFU, Uberlândia, MG, Brazil., Alves de Melo Fernandes T; Laboratory of Biochemistry and Animal Toxins, Institute of Biotechnology, Federal University of Uberlândia - UFU, Uberlândia, MG, Brazil., Correia LIV; Laboratory of Biochemistry and Animal Toxins, Institute of Biotechnology, Federal University of Uberlândia - UFU, Uberlândia, MG, Brazil., Borges BC; Laboratory of Osteoimmunology and Tumor Immunology, Institute of Biomedical Sciences, Federal University of Uberlândia - UFU, Uberlândia, MG, Brazil., Teixeira SC; Laboratory of Biochemistry and Animal Toxins, Institute of Biotechnology, Federal University of Uberlândia - UFU, Uberlândia, MG, Brazil., Silva MJB; Laboratory of Osteoimmunology and Tumor Immunology, Institute of Biomedical Sciences, Federal University of Uberlândia - UFU, Uberlândia, MG, Brazil., Amorim FG; Laboratory of Mass Spectrometry, Department of Chemistry, University of Liège, Liège, Belgium., Quinton L; Laboratory of Mass Spectrometry, Department of Chemistry, University of Liège, Liège, Belgium., Saraiva AL; Laboratory of Biochemistry and Molecular Biology, Institute of Biotechnology, Federal University of Uberlândia - UFU, Uberlândia, MG, Brazil., Espindola FS; Laboratory of Biochemistry and Molecular Biology, Institute of Biotechnology, Federal University of Uberlândia - UFU, Uberlândia, MG, Brazil., Iwai LK; Laboratory of Applied Toxinology (LETA) and Center of Toxins, Immune-Response and Cell Signaling (CeTICS), Butantan Institute, São Paulo, SP, Brazil., Rodrigues RS; Laboratory of Biochemistry and Animal Toxins, Institute of Biotechnology, Federal University of Uberlândia - UFU, Uberlândia, MG, Brazil., Yoneyama KAG; Laboratory of Biochemistry and Animal Toxins, Institute of Biotechnology, Federal University of Uberlândia - UFU, Uberlândia, MG, Brazil., de Melo Rodrigues Ávila V; Laboratory of Biochemistry and Animal Toxins, Institute of Biotechnology, Federal University of Uberlândia - UFU, Uberlândia, MG, Brazil. Electronic address: veridiana@ufu.br.
Jazyk: angličtina
Zdroj: Toxicon : official journal of the International Society on Toxinology [Toxicon] 2023 Jul; Vol. 230, pp. 107156. Date of Electronic Publication: 2023 May 09.
DOI: 10.1016/j.toxicon.2023.107156
Abstrakt: This study reports the isolation of CollinLAAO-I, a new L-amino acid oxidase from Crotalus durissus collilineatus snake venom, its biochemical characterization and leishmanicidal potential in Leishmania spp. CollinLAAO-I (63.1 kDa) was successfully isolated with high purity using two chromatographic steps and represents 2.5% of total venom proteins. CollinLAAO-I displayed high enzymatic activity (4262.83 U/mg/min), significantly reducing after 28 days. The enzymatic activity of CollinLAAO-I revealed higher affinity for hydrophobic amino acids such as L-leucine, high enzymatic activity in a wide pH range (6.0-10.0), at temperatures from 0 to 25 °C, and showed complete inhibition in the presence of Na + and K + . Cytotoxicity assays revealed IC 50 of 18.49 and 11.66 μg/mL for Leishmania (L.) amazonensis and Leishmania (L.) infantum, respectively, and the cytotoxicity was completely suppressed by catalase. CollinLAAO-I significantly increased the intracellular concentration of reactive oxygen species (ROS) and reduced the mitochondrial potential of both Leishmania species. Furthermore, CollinLAAO-I decreased the parasite capacity to infect macrophages by around 70%, indicating that even subtoxic concentrations of CollinLAAO-I can interfere with Leishmania vital processes. Thus, the results obtained for CollinLAAO-I provide important support for developing therapeutic strategies against leishmaniasis.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: