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1.
PLoS Genet ; 11(11): e1005642, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26540204

RESUMO

During development, certain Drosophila sensory neurons undergo dendrite pruning that selectively eliminates their dendrites but leaves the axons intact. How these neurons regulate pruning activity in the dendrites remains unknown. Here, we identify a coiled-coil protein Spindle-F (Spn-F) that is required for dendrite pruning in Drosophila sensory neurons. Spn-F acts downstream of IKK-related kinase Ik2 in the same pathway for dendrite pruning. Spn-F exhibits a punctate pattern in larval neurons, whereas these Spn-F puncta become redistributed in pupal neurons, a step that is essential for dendrite pruning. The redistribution of Spn-F from puncta in pupal neurons requires the phosphorylation of Spn-F by Ik2 kinase to decrease Spn-F self-association, and depends on the function of microtubule motor dynein complex. Spn-F is a key component to link Ik2 kinase to dynein motor complex, and the formation of Ik2/Spn-F/dynein complex is critical for Spn-F redistribution and for dendrite pruning. Our findings reveal a novel regulatory mechanism for dendrite pruning achieved by temporal activation of Ik2 kinase and dynein-mediated redistribution of Ik2/Spn-F complex in neurons.


Assuntos
Dendritos/fisiologia , Proteínas de Drosophila/fisiologia , Quinase I-kappa B/metabolismo , Células Receptoras Sensoriais/citologia , Animais , Citoplasma/metabolismo , Proteínas de Drosophila/metabolismo , Drosophila melanogaster , Dineínas/metabolismo , Fosforilação
2.
J Leukoc Biol ; 93(5): 723-35, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23431043

RESUMO

Early studies have demonstrated the ability of dietary carotenoids to enhance immune response, but the mechanism underlying their influence on macrophage activity remains unclear. Here, we investigated the effects of carotenoids on macrophage activity. Carotenoids, including lutein and lycopene, enhanced MMP-9 activity in RAW264.7 macrophages. Lutein was chosen as a representative and analyzed further in this study. It increased the synthesis, activity, and release of MMP-9 in murine RAW264.7 and primary-cultured peritoneal macrophages. MMP-9 induction by lutein was through the transcriptional regulation of mmp-9. It was blunted by the MAPK inhibitors targeting ERK1/2 and p38 MAPK, the reagents that inhibit free radical signaling, and the inhibitors and siRNA targeting RARß. Moreover, lutein induced Nox activation and intracellular ROS production at an early stage of treatment. This carotenoid also caused ERK1/2 and p38 MAPK activation, RARß expression, and RAR interaction with its responsive element in the promoter region. These findings suggest the involvement of ROS, MAPKs, and RARß activation in lutein-driven MMP-9 expression and release. Interestingly, lutein enhanced the phagocytic activity of macrophages, and the secreted MMP-9 appeared to be involved in this process. In summary, we provide evidence here for the first time that the carotenoid lutein induces intracellular ROS generation and MAPK and RARß activation in macrophages, leading to an increase in MMP-9 release and macrophage phagocytosis. Our results demonstrate that lutein exerts an immunomodulatory effect on macrophages.


Assuntos
MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Luteína/farmacologia , Macrófagos/efeitos dos fármacos , Metaloproteinase 9 da Matriz/biossíntese , Fagocitose/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Receptores do Ácido Retinoico/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Animais , Células Cultivadas , Ativação Enzimática , Humanos , Macrófagos/metabolismo , Camundongos , Camundongos Endogâmicos ICR , Receptores X de Retinoides/fisiologia
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