Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/26277
Title: Knockdown of host antioxidant defense genes enhances the effect of Glucantime on intracellular Leishmania braziliensis in Human Macrophages
Authors: Téllez, Jair
Romero, Ibeth
Soares, Maurilio José
Steindel, Mario
Romanha, Alvaro José
Affilliation: Universidade Federal de Santa Catarina. Centro de Ciências Biológicas. Departamento de Microbiologia, Imunologia e Parasitologia. Laboratório de Protozoologia. Florianópolis, SC, Brasil. / Universidade Federal de Santa Catarina. Centro de Ciências Biológicas. Programa de Pós-Graduação em Biotecnologia e Biociências. Florianópolis, SC, Brasil.
Universidade Federal de Santa Catarina. Centro de Ciências Biológicas. Departamento de Microbiologia, Imunologia e Parasitologia. Laboratório de Protozoologia. Florianópolis, SC, Brasil. / Universidade Federal de Santa Catarina. Centro de Ciências Biológicas. Programa de Pós-Graduação em Biotecnologia e Biociências. Florianópolis, SC, Brasil.
Fundação Oswaldo Cruz. Instituto Carlos Chagas. Laboratório de Biologia Celular. Curitiba, PR, Brasil.
Universidade Federal de Santa Catarina. Centro de Ciências Biológicas. Departamento de Microbiologia, Imunologia e Parasitologia. Laboratório de Protozoologia. Florianópolis, SC, Brasil. / Universidade Federal de Santa Catarina. Centro de Ciências Biológicas. Programa de Pós-Graduação em Biotecnologia e Biociências. Florianópolis, SC, Brasil.
Universidade Federal de Santa Catarina. Centro de Ciências Biológicas. Departamento de Microbiologia, Imunologia e Parasitologia. Laboratório de Protozoologia. Florianópolis, SC, Brasil. / Universidade Federal de Santa Catarina. Centro de Ciências Biológicas. Programa de Pós-Graduação em Biotecnologia e Biociências. Florianópolis, SC, Brasil.
Abstract: Leishmaniasis is a neglected tropical disease that affects millions of people worldwide and represents a major public health problem. Information on protein expression patterns and functional roles within the context of Leishmania-infected human monocyte-derived macrophages (MDMs) under drug treatment conditions is essential for understanding the role of these cells in leishmaniasis treatment. We analyzed functional changes in the expression of human MDM genes and proteins during in vitro infection by Leishmania braziliensis and treatment with Glucantime (SbV), using quantitative PCR (qPCR) arrays, Western blotting, confocal microscopy, and small interfering RNA (siRNA) human gene inhibition assays. Comparison of the results from gene transcription and protein expression analyses revealed that glutathione S-transferase π1 (GSTP1), glutamate-cysteine ligase modifier subunit (GCLM), glutathione reductase (GSR), glutathione synthetase (GSS), thioredoxin (TRX), and ATP-binding cassette, subfamily B, member 5 (ABCB5), were strongly upregulated at both the mRNA and protein levels in human MDMs that were infected and treated, compared to the control group. Subcellular localization studies showed a primarily phagolysosomal location for the ABCB5 transporter, indicating that this protein may be involved in the transport of SbV By inducing a decrease in L. braziliensis intracellular survival in THP-1 macrophages, siRNA silencing of GSTP1, GSS, and ABCB5 resulted in an increased leishmanicidal effect of SbV exposure in vitro Our results suggest that human MDMs infected with L. braziliensis and treated with SbV express increased levels of genes participating in antioxidant defense, whereas our functional analyses provide evidence for the involvement of human MDMs in drug detoxification. Therefore, we conclude that GSS, GSTP1, and ABCB5 proteins represent potential targets for enhancing the leishmanicidal activity of Glucantime.
Keywords: Leishmaniasis
Host-Pathogen Interactions
Glutathione S-Transferase pi
Glutathione Synthase
Macrophages
Keywords in spanish: Leishmaniasis
Interacciones Huésped-Patógeno
Gutatión-S-Transferasa pi
Glutatión Sintasa
Macrófagos
keywords: Leishmania braziliensis
DeCS: Leishmaniose
Interações Hospedeiro-Patógeno
Glutationa S-Transferase pi
Glutationa Sintase
Macrófagos
Issue Date: 2017
Publisher: American Society for Microbiology
Citation: TÉLLEZ, Jair et al. Knockdown of host antioxidant defense genes enhances the effect of Glucantime on intracellular Leishmania braziliensis in Human Macrophages. Antimicrobial Agents and Chemotherapy, v. 61, n. 7, p.1-16, 2017.
DOI: 10.1128/AAC.02099-16
ISSN: 1098-6596
Copyright: open access
Appears in Collections:PR - ICC - Artigos de Periódicos

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