Ptaquiloside reduces NK cell activities by enhancing metallothionein expression, which is prevented by selenium

Autor(es)

Latorre, Andreia O. ^[1] ; Caniceiro, Beatriz D. ^[1] ; Fukumasu, Heidge ^[2] ; Gardner, Dale R. ^[3] ; Lopes, Fabricio M. ; Wysochi, Jr., Harry L. ^[4] ; da Silva, Tereza C. ^[1] ; Haraguchi, Mitsue ^[4] ; Bressan, Fabiana F. ^[2] ; Gorniak, Silvana L. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Sch Vet Med & Anim Sci, Dept Pathol, BR-05508270 Sao Paulo - Brazil

^[2] Univ Sao Paulo, Sch Anim Sci & Food Engn, Dept Basic Sci, BR-13635900 Pirassununga, SP - Brazil

^[3] Poisonous Plant Res Lab, N Logan, UT 84341 - USA

^[4] Biol Inst Sao Paulo, BR-04014002 Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Toxicology; v. 304, p. 100-108, FEB 8 2013.
• Citações Web of Science: 8

Resumo

Pteridium aquilinum, one of the most important poisonous plants in the world, is known to be carcinogenic to animals and humans. Moreover, our previous studies showed that the immunosuppressive effects of ptaquiloside, its main toxic agent, were prevented by selenium in mouse natural killer (NK) cells. We also verified that this immunosuppression facilitated development of cancer. Here, we performed gene expression microarray analysis in splenic NK cells from mice treated for 14 days with ptaquiloside (5.3 mg/kg) and/or selenium (1.3 mg/kg) to identify gene transcripts altered by ptaquiloside that could be linked to the immunosuppression and that would be prevented by selenium. Transcriptome analysis of ptaquiloside samples revealed that 872 transcripts were expressed differentially (fold change>2 and p<0.05), including 77 up-regulated and 795 down-regulated transcripts. Gene ontology analysis mapped these up-regulated transcripts to three main biological processes (cellular ion homeostasis, negative regulation of apoptosis and regulation of transcription). Considering the immunosuppressive effect of ptaquiloside, we hypothesized that two genes involved in cellular ion homeostasis, metallothionein 1 (Mt1) and metallothionein 2 (Mt2), could be implicated because Mt1 and Mt2 are responsible for zinc homeostasis, and a reduction of free intracellular zinc impairs NK functions. We confirm these hypotheses and show increased expression of metallothionein in splenic NK cells and reduction in free intracellular zinc following treatment with ptaquiloside that were completely prevented by selenium co-treatment. These findings could help avoid the higher susceptibility to cancer that is induced by P. aquilinum-mediated immunosuppressive effects. (C) 2012 Elsevier Ireland Ltd. All rights reserved. (AU)

• Processo FAPESP: 07/50313-4 - Avaliação dos efeitos imunomodulatórios da Pteridium aquilinum na resposta imune celular: estudo em camundongos
• Beneficiário: Andréia Oliveira Latorre
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 10/52186-2 - I. avaliacao dos mecanismos moleculares da imunotoxicidade e carcinogenicidade da pteridium aquilinum. ii. avaliacao do mecanismo de reversao da imunotoxicidade pela suplementacao com selenio
• Beneficiário: Andréia Oliveira Latorre
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado