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2050-01-01
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A PROTEOMIC INSIGHT INTO THE EFFECTS OF THE IMMUNOMODULATORY HYDROXYNAPHTHOQUINONE LAPACHOL ON ACTIVATED MACROPHAGES
Macrófagos ativados
Separação de proteínas
Níveis de proteína
Análise comparativa
Linha Celular, Tumor
Movimento Celular / efeitos de drogas
Citosol / metabolismo
Humanos
Interferona-gama / imunologia
Ativação de macrófagos / efeitos de drogas
Macrófagos / efeitos de drogas
Macrófagos / metabolismo
Proteínas de Membrana / metabolismo
Naftoquinonas / farmacologia
Fagocitose / efeitos de drogas
Proteólise / efeitos de drogas
Proteômica
Receptor Toll-Like 2 / agonistas
Affilliation
Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Laboratório de Virologia e Terapia Experimental. Recife, PE, Brasil.
Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Laboratório de Virologia e Terapia Experimental. Recife, PE, Brasil.
Central South University. Molecular Biology Research Center. School of Biological Science and Technology. Changsha, Hunan, China.
International Centre for Genetic Engineering and Biotechnology. Area Science Park. Leukocyte Biology Group. Trieste, Italy.
Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Laboratório de Virologia e Terapia Experimental. Recife, PE, Brasil.
Central South University. Molecular Biology Research Center. School of Biological Science and Technology. Changsha, Hunan, China.
International Centre for Genetic Engineering and Biotechnology. Area Science Park. Leukocyte Biology Group. Trieste, Italy.
Abstract
We report the effect of an immunomodulatory and anti-mycobacterial naphthoquinone, lapachol, on the bi-dimensional patterns of protein expression of toll-like receptor 2 (TLR2)-agonised and IFN-γ-treated THP-1 macrophages. This non-hypothesis driven proteomic analysis intends to shed light on the cellular functions lapachol may be affecting. Proteins of both cytosol and membrane fractions were analysed. After quantification of the protein spots, the protein levels corresponding to macrophages activated in the absence or presence of lapachol were compared. A number of proteins were identified, the levels of which were appreciably and significantly increased or decreased as a result of the action of lapachol on the activated macrophages: cofilin-1, fascin, plastin-2, glucose-6-P-dehydrogenase, adenylyl cyclase-associated protein 1, pyruvate kinase, sentrin-specific protease 6, cathepsin B, cathepsin D, cytosolic aminopeptidase, proteasome β type-4 protease, tryptophan-tRNA ligase, DnaJ homolog and protein disulphide isomerase. Altogether, the comparative analysis performed indicates that lapachol could be hypothetically causing an impairment of cell migration and/or phagocytic capacity, an increase in NADPH availability, a decrease in pyruvate concentration, protection from proteosomal protein degradation, a decrease in lysosomal protein degradation, an impairment of cytosolic peptide generation, and an interference with NOS2 activation and grp78 function. The present proteomic results suggest issues that should be experimentally addressed ex- and in-vivo, to establish more accurately the potential of lapachol as an anti-infective drug. This study also constitutes a model for the pre-in-vivo evaluation of drug actions.
Keywords in Portuguese
LapacholMacrófagos ativados
Separação de proteínas
Níveis de proteína
Análise comparativa
DeCS
Antibacterianos / farmacologiaLinha Celular, Tumor
Movimento Celular / efeitos de drogas
Citosol / metabolismo
Humanos
Interferona-gama / imunologia
Ativação de macrófagos / efeitos de drogas
Macrófagos / efeitos de drogas
Macrófagos / metabolismo
Proteínas de Membrana / metabolismo
Naftoquinonas / farmacologia
Fagocitose / efeitos de drogas
Proteólise / efeitos de drogas
Proteômica
Receptor Toll-Like 2 / agonistas
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