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Métodos Terapêuticos e Terapias MTCI
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1.
Metallomics ; 14(10)2022 10 08.
Artigo em Inglês | MEDLINE | ID: mdl-36138538

RESUMO

Nickel (Ni) is an essential yet toxic trace element. Although a cofactor for many metalloenzymes, nickel function and metabolism is not fully explored in eukaryotes. Molecular biology and metallomic methods were utilized to explore the new physiological functions of nickel in Saccharomyces cerevisiae. Here we showed that MTM1 knockout cells displayed much stronger nickel tolerance than wild-type cells and mitochondrial accumulations of Ni and Fe of mtm1Δ cells dramatically decreased compared to wild-type cells when exposed to excess nickel. Superoxide dismutase 2 (Sod2p) activity in mtm1Δ cells was severely attenuated and restored through Ni supplementation in media or total protein. SOD2 mRNA level of mtm1Δ cells was significantly higher than that in the wild-type strain but was decreased by Ni supplementation. MTM1 knockout afforded resistance to excess nickel mediated through reactive oxygen species levels. Meanwhile, additional Ni showed no significant effect on the localization of Mtm1p. Our study reveals the MTM1 gene plays an important role in nickel homeostasis and identifies a novel function of nickel in promoting Sod2p activity in yeast cells.


Assuntos
Metaloproteínas , Proteínas de Saccharomyces cerevisiae , Oligoelementos , Proteínas de Transporte/metabolismo , Metaloproteínas/metabolismo , Proteínas Mitocondriais/metabolismo , Níquel/metabolismo , Níquel/toxicidade , RNA Mensageiro/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo , Oligoelementos/metabolismo
2.
Macromol Rapid Commun ; 31(2): 228-36, 2010 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-21590896

RESUMO

In this work, we describe the preparation and biomedical functionalities of complex nanoparticle assemblies with magnetoplasmonic properties suitable for simultaneous cancer therapy and diagnostics (theranostics). Most commonly magnetoplasmonic nanostructures are made by careful adaptation of metal reduction protocols which is both tedious and restrictive. Here we apply the strategy of nanoscale assemblies to prepare such systems from individual building blocks. The prepared superstructures are based on magnetic Fe(3) O(4) nanoparticles encapsulated in silica shell representing the magnetic module. The cores are surrounded in a corona-like fashion by gold nanoparticles representing the plasmonic module. As additional functionality they were also coated by poly(ethyleneglycol) chains as a cloaking agent to extend the blood circulation time. The preparation is exceptionally simple and allows one to vary the contribution of each function. Both modules can carry drugs and, in this study, they were loaded with the potential anticancer drug curcumin. A comprehensive set of microscopy, spectroscopy and biochemical methods were applied to characterize both imaging and therapeutic function of the nanoparticle assemblies against leukemia HL-60 cells. High contrast magnetic resonance images and high apoptosis rates demonstrate the success of assembly approach for the preparation of magnetoplasmonic nanoparticles. This technology allows one to easily "dial in" the functionalities in the clinical setting for personalized theranostic regiments.

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