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1.
Nanotechnology ; 33(24)2022 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-35259735

RESUMEN

Clean water is vital for healthy ecosystems, for human life and, in a broader sense, it is directly linked to our socio-economic development. Nevertheless, climate change, pollution and increasing world population will likely make clean water scarcer in the near future. Consequently, it becomes imperative to develop novel materials and more efficient ways of treating waste and contaminated water. Carbon nanotube (CNT) sponges, for example, are excellent in removing oleophilic contaminants; however, due to their super-hydrophobic nature, they are not as efficient when it comes to absorbing water-soluble substances. Here, by means of a scalable method consisting of simply treating CNT sponges at mild temperatures in air, we attach oxygen-containing functional groups to the CNT surface. The functionalized sponge becomes hydrophilic while preserving its micro- and macro-structure and can therefore be used to successfully remove toxic contaminants, such as pesticides, that are dissolved in water. This discovery expands the current range of applications of CNT sponges to those fields in which a hydrophilic character of the sponge is more suitable.

2.
Int J Mol Sci ; 23(3)2022 Jan 26.
Artículo en Inglés | MEDLINE | ID: mdl-35163332

RESUMEN

Vitamin D3, known to regulate bone homeostasis, has recently been shown to have many pleiotropic effects in different tissues and organs due to the presence of its receptor in a wide range of cells. Our previous study demonstrated that vitamin D3 was able to increase the wound healing respect to the control sample, 24 h after cutting, without however leading to a complete repair. The aim of the study was to combine vitamin D3 with silver nanoparticles to possibly enable a faster reparative effect. The results showed that this association was capable of inducing a complete wound healing only after 18 h. Moreover, a treatment of vitamin D3 + silver nanoparticles yielded a small percentage of keratinocytes vimentin-positive, suggesting the possibility that the treatment was responsible for epithelial to mesenchymal transition of the cells, facilitating wound healing repair. Since vitamin D3 acts via sphingolipid metabolism, we studied the expression of gene encoding for the metabolic enzymes and protein level. We found an increase in neutral sphingomyelinase without involvement of neutral ceramidase or sphingosine kinase2. In support, an increase in ceramide level was identified by Ultrafast Liquid Chromatography-Tandem Mass Spectrometry, suggesting a possible involvement of ceramides in wound healing process.


Asunto(s)
Colecalciferol , Nanopartículas del Metal , Supervivencia Celular , Ceramidas/metabolismo , Colecalciferol/metabolismo , Colecalciferol/farmacología , Transición Epitelial-Mesenquimal , Plata/farmacología
3.
Int J Mol Sci ; 22(17)2021 Aug 27.
Artículo en Inglés | MEDLINE | ID: mdl-34502192

RESUMEN

The release of exosomes can lead to cell-cell communication. Nutrients such as vitamin D3 and sphingolipids have important roles in many cellular functions, including proliferation, differentiation, senescence, and cancer. However, the specific composition of sphingolipids in exosomes and their changes induced by vitamin D3 treatment have not been elucidated. Here, we initially observed neutral sphingomyelinase and vitamin D receptors in exosomes released from HN9.10 embryonic hippocampal cells. Using ultrafast liquid chromatography tandem mass spectrometry, we showed that exosomes are rich in sphingomyelin species compared to whole cells. To interrogate the possible functions of vitamin D3, we established the optimal conditions of cell treatment and we analyzed exosome composition. Vitamin D3 was identified as responsible for the vitamin D receptor loss, for the increase in neutral sphingomyelinase content and sphingomyelin changes. As a consequence, the generation of ceramide upon vitamin D3 treatment was evident. Incubation of the cells with neutral sphingomyelinase, or the same concentration of ceramide produced in exosomes was necessary and sufficient to stimulate embryonic hippocampal cell differentiation, as vitamin D3. This is the first time that exosome ceramide is interrogated for mediate the effect of vitamin D3 in inducing cell differentiation.


Asunto(s)
Diferenciación Celular , Ceramidas/metabolismo , Colecalciferol/farmacología , Exosomas/metabolismo , Hipocampo/metabolismo , Vitaminas/farmacología , Células Cultivadas , Exosomas/efectos de los fármacos , Hipocampo/efectos de los fármacos , Hipocampo/embriología , Humanos , Receptores de Calcitriol/metabolismo , Esfingomielina Fosfodiesterasa/metabolismo
4.
J Am Chem Soc ; 142(2): 999-1009, 2020 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-31794194

RESUMEN

Metal-organic frameworks (MOFs) show great prospect as catalysts and catalyst support materials. Yet, studies that address their dynamic, kinetic, and mechanistic role in target reactions are scarce. In this study, an exceptionally stable MOF catalyst consisting of Pt nanoparticles (NPs) embedded in a Zr-based UiO-67 MOF was subject to steady-state and transient kinetic studies involving H/D and 13C/12C exchange, coupled with operando infrared spectroscopy and density functional theory (DFT) modeling, targeting methanol formation from CO2/H2 feeds at 170 °C and 1-8 bar pressure. The study revealed that methanol is formed at the interface between the Pt NPs and defect Zr nodes via formate species attached to the Zr nodes. Methanol formation is mechanistically separated from the formation of coproducts CO and methane, except for hydrogen activation on the Pt NPs. Careful analysis of transient data revealed that the number of intermediates was higher than the number of open Zr sites in the MOF lattice around each Pt NP. Hence, additional Zr sites must be available for formate formation. DFT modeling revealed that Pt NP growth is sufficiently energetically favored to enable displacement of linkers and creation of open Zr sites during pretreatment. However, linker displacement during formate formation is energetically disfavored, in line with the excellent catalyst stability observed experimentally. Overall, the study provides firm evidence that methanol is formed at the interface of Pt NPs and linker-deficient Zr6O8 nodes resting on the Pt NP surface.

5.
J Am Chem Soc ; 142(40): 17105-17118, 2020 Oct 07.
Artículo en Inglés | MEDLINE | ID: mdl-32902970

RESUMEN

In catalysts for CO2 hydrogenation, the interface between metal nanoparticles (NPs) and the support material is of high importance for the activity and reaction selectivity. In Pt NP-containing UiO Zr-metal-organic frameworks (MOFs), key intermediates in methanol formation are adsorbed at open Zr-sites at the Pt-MOF interface. In this study, we investigate the dynamic role of the Zr-node and the influence of H2O on the CO2 hydrogenation reaction at 170 °C, through steady state and transient isotope exchange experiments, H2O cofeed measurements, and density functional theory (DFT) calculations. The study revealed that an increased number of Zr-node defects increase the formation rates to both methanol and methane. Transient experiments linked the increase to a higher number of surface intermediates for both products. Experiments involving either dehydrated or prehydrated Zr-nodes showed higher methanol and methane formation rates over the dehydrated Zr-node. Transient experiments suggested that the difference is related to competitive adsorption between methanol and water. DFT calculations and microkinetic modeling support this conclusion and give further insight into the equilibria involved in the competitive adsorption process. The calculations revealed weaker adsorption of methanol in defective or dehydrated nodes, in agreement with the larger gas phase concentration of methanol observed experimentally. The microkinetic model shows that [Zr2(µ-O)2]4+ and [Zr2(µ-OH)(µ-O)(OH)(H2O)]4+ are the main surface species when the concentration of water is lower than the number of defect sites. Lastly, although addition of water was found to promote methanol desorption, water does not change the methanol steady state reaction rate, while it has a substantial inhibiting effect on CH4 formation. These results indicate that water can be used to increase the reaction selectivity to methanol and encourages further detailed investigations of the catalyst system.

6.
Artículo en Inglés | MEDLINE | ID: mdl-30928412

RESUMEN

Both sphingomyelinase and Toll-Like Receptor 4 (TLR4) are implicated in neurodegenerative diseases. However, the relationship between the two molecules remains unclear. In this study, using WT and TLR4-deficient mice, treated or not with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), we aimed to investigate the relation between TLR4 and neutral sphingomyelinase (nSMase) in the midbrain. We found that the lack of TLR4 caused increase in nSMase protein expression and enzyme activity in the midbrain, as well as a marked delocalization from the cell membranes. This provoked a decrease in sphingomyelin (SM) species and an increase in ceramide levels. We found that exposure of TLR4-deficient mice to MPTP reduces unsaturated SM species by increasing saturated/unsaturated SM ratio. Saturated fatty acid make SM more rigid and could contribute to reducing neural plasticity. In this study we showed that the absence of TLR4 also induced reduction of both heavy neurofilaments and glial fibrillary acidic protein (GFAP) and mice exhibited higher sensitivity to MPTP administration. We speculated about the possible association between nSMase-TLR4 complex and MPTP midbrain damage. Taken together, our findings provide for the first time indications about the role of TLR4 in change of SM metabolism in MPTP neurotoxicity.


Asunto(s)
Intoxicación por MPTP/metabolismo , Esfingomielina Fosfodiesterasa/metabolismo , Receptor Toll-Like 4/deficiencia , Animales , Intoxicación por MPTP/enzimología , Intoxicación por MPTP/patología , Mesencéfalo/metabolismo , Mesencéfalo/patología , Ratones , Esfingomielinas/metabolismo
7.
Chemphyschem ; 19(4): 484-495, 2018 Feb 19.
Artículo en Inglés | MEDLINE | ID: mdl-29250897

RESUMEN

Substituting metals for either aluminum or phosphorus in crystalline, microporous aluminophosphates creates Brønsted acid sites, which are well known to catalyze several key reactions, including the methanol to hydrocarbons (MTH) reaction. In this work, we synthesized a series of metal-substituted aluminophosphates with AFI topology that differed primarily in their acid strength and that spanned a predicted range from high Brønsted acidity (H-MgAlPO-5, H-CoAlPO-5, and H-ZnAlPO-5) to medium acidity (H-SAPO-5) and low acidity (H-TiAlPO-5 and H-ZrAlPO-5). The synthesis was aimed to produce materials with homogenous properties (e.g. morphology, crystallite size, acid-site density, and surface area) to isolate the influence of metal substitution. This was verified by extensive characterization. The materials were tested in the MTH reaction at 450 °C by using dimethyl ether (DME) as feed. A clear activity difference was found, for which the predicted stronger acids converted DME significantly faster than the medium and weak Brønsted acidic materials. Furthermore, the stronger Brønsted acids (Mg, Co and Zn) produced more light alkenes than the weaker acids. The weaker acids, especially H-SAPO-5, produced more aromatics and alkanes, which indicates that the relative rates of competing reactions change upon decreasing the acid strength.

8.
Faraday Discuss ; 208(0): 187-205, 2018 09 03.
Artículo en Inglés | MEDLINE | ID: mdl-29876557

RESUMEN

The formation of palladium hydride and carbide phases in palladium-based catalysts is a critical process that changes the catalytic performance and selectivity of the catalysts in important industrial reactions, such as the selective hydrogenation of alkynes or alkadienes. We present a comprehensive study of a 5 wt% carbon supported Pd nanoparticle (NP) catalyst in various environments by using in situ and operando X-ray absorption spectroscopy and diffraction, to determine the structure and evolution of palladium hydride and carbide phases, and their distribution throughout the NPs. We demonstrate how the simultaneous analysis of extended X-ray absorption fine structure (EXAFS) spectra and X-ray powder diffraction (XRPD) patterns allows discrimination between the inner "core" and outer "shell" regions of the NP during hydride phase formation at different temperatures and under different hydrogen pressures, indicating that the amount of hydrogen in the shell region of the NP is lower than that in the core. For palladium carbide, advanced analysis of X-ray absorption near-edge structure (XANES) spectra allows the detection of Pd-C bonds with carbon-containing molecules adsorbed at the surface of the NPs. In addition, H/Pd and C/Pd stoichiometries of PdHx and PdCy phases were obtained by using theoretical modelling and fitting of XANES spectra. Finally, the collection of operando time-resolved XRPD patterns (with a time resolution of 5 s) allowed the detection, during the ethylene hydrogenation reaction, of periodic oscillations in the NPs core lattice parameter, which were in phase with the MS signal of ethane (product) and in antiphase with the MS signal of H2 (reactant), highlighting an interesting direct structure-reactivity relationship. The presented studies show how a careful combination of X-ray absorption and diffraction can differentiate the structure of the core, shell and surface of the palladium NPs under working conditions and prove their relevant roles in catalysis.

9.
Faraday Discuss ; 208(0): 287-306, 2018 09 03.
Artículo en Inglés | MEDLINE | ID: mdl-29796547

RESUMEN

Functionalization of metal-organic frameworks with metal nanoparticles (NPs) is a promising way for producing advanced materials for catalytic applications. We present the synthesis and in situ characterization of palladium NPs encapsulated inside a functionalized UiO-67 metal-organic framework. The initial structure was synthesized with 10% of PdCl2bpydc moieties with grafted Pd ions replacing standard 4,4'-biphenyldicarboxylate linkers. This material exhibits the same high crystallinity and thermal stability of standard UiO-67. Formation of palladium NPs was initiated by sample activation in hydrogen and monitored by in situ X-ray powder diffraction and X-ray absorption spectroscopy (XAS). The reduction of PdII ions to Pd0 occurs above 200 °C in 6% H2/He flow. The formed palladium NPs have an average size of 2.1 nm as limited by the cavities of UiO-67 structure. The resulting material showed high activity towards ethylene hydrogenation. Under reaction conditions, palladium was found to form a carbide structure indicated by operando XAS, while formation of ethane was monitored by mass spectroscopy and infra-red spectroscopy.

10.
Int J Mol Sci ; 19(11)2018 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-30388783

RESUMEN

Daunorubicin is an anticancer drug, and cholesterol is involved in cancer progression, but their relationship has not been defined. In this study, we developed a novel experimental model that utilizes daunorubicin, cholesterol, and daunorubicin plus cholesterol in the same cells (H35) to search for the role of nuclear lipid microdomains, rich in cholesterol and sphingomyelin, in drug resistance. We find that the daunorubicin induces perturbation of nuclear lipid microdomains, localized in the inner nuclear membrane, where active chromatin is anchored. As changes of sphingomyelin species in nuclear lipid microdomains depend on neutral sphingomyelinase activity, we extended our studies to investigate whether the enzyme is modulated by daunorubicin. Indeed the drug stimulated the sphingomyelinase activity that induced reduction of saturated long chain fatty acid sphingomyelin species in nuclear lipid microdomains. Incubation of untreated-drug cells with high levels of cholesterol resulted in the inhibition of sphingomyelinase activity with increased saturated fatty acid sphingomyelin species. In daunodubicin-treated cells, incubation with cholesterol reversed the action of the drug by acting via neutral sphingomyelinase. In conclusion, we suggest that cholesterol and sphingomyelin-forming nuclear lipid microdomains are involved in the drug resistance.


Asunto(s)
Carcinoma Hepatocelular/patología , Núcleo Celular/metabolismo , Daunorrubicina/farmacología , Resistencia a Antineoplásicos/efectos de los fármacos , Neoplasias Hepáticas/patología , Microdominios de Membrana/metabolismo , Línea Celular Tumoral , Núcleo Celular/efectos de los fármacos , Colesterol/metabolismo , Regulación hacia Abajo/efectos de los fármacos , Proteínas de la Matriz de Golgi/metabolismo , Humanos , Lamina Tipo B/metabolismo , Microdominios de Membrana/efectos de los fármacos , Factor de Transcripción STAT3/metabolismo , Esfingomielina Fosfodiesterasa/metabolismo , Esfingomielinas/metabolismo
11.
Mediators Inflamm ; 2017: 2470950, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-29343884

RESUMEN

Neutral sphingomyelinase is known to be implicated in growth arrest, differentiation, proliferation, and apoptosis. Although previous studies have reported the involvement of neutral sphingomyelinase in hippocampus physiopathology, its behavior in the hippocampus during Parkinson's disease remains undetected. In this study, we show an upregulation of inducible nitric oxide synthase and a downregulation of neutral sphingomyelinase in the hippocampus of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine- (MPTP-) induced mouse model of Parkinson's disease. Moreover, the stimulation of neutral sphingomyelinase activity with vitamin 1,25-dihydroxyvitamin D3 reduces specifically saturated fatty acid sphingomyelin by making sphingomyelin a less rigid molecule that might influence neurite plasticity. The possible biological relevance of the increase of neutral sphingomyelinase in Parkinson's disease is discussed.


Asunto(s)
Hipocampo/enzimología , Enfermedad de Parkinson Secundaria/inducido químicamente , Enfermedad de Parkinson Secundaria/enzimología , Esfingomielina Fosfodiesterasa/metabolismo , Animales , Calcitriol/farmacología , Línea Celular , Modelos Animales de Enfermedad , Hipocampo/efectos de los fármacos , Hipocampo/patología , Mediadores de Inflamación/metabolismo , Intoxicación por MPTP/enzimología , Masculino , Ratones , Ratones Endogámicos C57BL , Óxido Nítrico Sintasa de Tipo II/metabolismo , Enfermedad de Parkinson Secundaria/patología , Esfingomielinas/metabolismo
12.
Int J Mol Sci ; 18(5)2017 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-28445397

RESUMEN

Radiation-induced damage is a complex network of interlinked signaling pathways, which may result in apoptosis, cell cycle arrest, DNA repair, and cancer. The development of thyroid cancer in response to radiation, from nuclear catastrophes to chemotherapy, has long been an object of study. A basic overview of the ionizing and non-ionizing radiation effects of the sensitivity of the thyroid gland on radiation and cancer development has been provided. In this review, we focus our attention on experiments in cell cultures exposed to ionizing radiation, ultraviolet light, and proton beams. Studies on the involvement of specific genes, proteins, and lipids are also reported. This review also describes how lipids are regulated in response to the radiation-induced damage and how they are involved in thyroid cancer etiology, invasion, and migration and how they can be used as both diagnostic markers and drug targets.


Asunto(s)
Radiación Ionizante , Neoplasias de la Tiroides/etiología , Animales , Apoptosis/efectos de la radiación , Biomarcadores/metabolismo , Humanos , Metabolismo de los Lípidos/efectos de la radiación , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal/efectos de la radiación , Glándula Tiroides/patología , Glándula Tiroides/efectos de la radiación , Rayos Ultravioleta
13.
Int J Mol Sci ; 18(5)2017 May 04.
Artículo en Inglés | MEDLINE | ID: mdl-28471415

RESUMEN

Physical and mental health requires a correct functioning of the thyroid gland, which controls cardiovascular, musculoskeletal, nervous, and immune systems, and affects behavior and cognitive functions. Microgravity, as occurs during space missions, induces morphological and functional changes within the thyroid gland. Here, we review relevant experiments exposing cell cultures (normal and cancer thyroid cells) to simulated and real microgravity, as well as wild-type and transgenic mice to hypergravity and spaceflight conditions. Well-known mechanisms of damage are presented and new ones, such as changes of gene expression for extracellular matrix and cytoskeleton proteins, thyrocyte phenotype, sensitivity of thyrocytes to thyrotropin due to thyrotropin receptor modification, parafollicular cells and calcitonin production, sphingomyelin metabolism, and the expression and movement of cancer molecules from thyrocytes to colloids are highlighted. The identification of new mechanisms of thyroid injury is essential for the development of countermeasures, both on the ground and in space, against thyroid cancer. We also address the question whether normal and cancer cells show a different sensitivity concerning changes of environmental conditions.


Asunto(s)
Glándula Tiroides/citología , Neoplasias de la Tiroides/etiología , Ingravidez/efectos adversos , Animales , Humanos , Vuelo Espacial , Glándula Tiroides/patología , Glándula Tiroides/fisiología
14.
Lipids Health Dis ; 15: 4, 2016 Jan 12.
Artículo en Inglés | MEDLINE | ID: mdl-26754536

RESUMEN

BACKGROUND: Diet and obesity are recognized in the scientific literature as important risk factors for cancer development and progression. Hypercholesterolemia facilitates lymphoma lymphoblastic cell growth and in time turns in hypocholesterolemia that is a sign of tumour progression. The present study examined how and where the cholesterol acts in cancer cells when you reproduce in vitro an in vivo hypercholesterolemia condition. METHODS: We used non-Hodgkin's T cell human lymphoblastic lymphoma (SUP-T1 cell line) and we studied cell morphology, aggressiveness, gene expression for antioxidant proteins, polynucleotide kinase/phosphatase and actin, cholesterol and sphingomyelin content and finally sphingomyelinase activity in whole cells, nuclei and nuclear lipid microdomains. RESULTS: We found that cholesterol changes cancer cell morphology with the appearance of protrusions together to the down expression of ß-actin gene and reduction of ß-actin protein. The lipid influences SUP-T1 cell aggressiveness since stimulates DNA and RNA synthesis for cell proliferation and increases raf1 and E-cadherin, molecules involved in invasion and migration of cancer cells. Cholesterol does not change GRX2 expression but it overexpresses SOD1, SOD2, CCS, PRDX1, GSR, GSS, CAT and PNKP. We suggest that cholesterol reaches the nucleus and increases the nuclear lipid microdomains known to act as platform for chromatin anchoring and gene expression. CONCLUSION: The results imply that, in hypercholesterolemia conditions, cholesterol reaches the nuclear lipid microdomains where activates gene expression coding for antioxidant proteins. We propose the cholesterolemia as useful parameter to monitor in patients with cancer.


Asunto(s)
Núcleo Celular/metabolismo , Colesterol/sangre , Neoplasias Hematológicas/sangre , Neoplasias Hematológicas/patología , Microdominios de Membrana/metabolismo , Cadherinas/metabolismo , Línea Celular Tumoral , ADN/biosíntesis , Humanos , Leucemia-Linfoma Linfoblástico de Células Precursoras/sangre , Leucemia-Linfoma Linfoblástico de Células Precursoras/patología , ARN/biosíntesis , Esfingomielina Fosfodiesterasa/metabolismo , Quinasas raf/metabolismo
15.
Lipids Health Dis ; 15(1): 183, 2016 Oct 19.
Artículo en Inglés | MEDLINE | ID: mdl-27756324

RESUMEN

BACKGROUND: Sphingomyelin plays very important roles in cell function under physiological and pathological conditions. Physical and chemical stimuli produce reactive oxygen species that stimulate acid sphingomyelinase to induce apoptosis. Antioxidant plants of the traditional Chinese Pharmacopoeia, such as Lycium Barbarum and Lycium Chinense, have become increasingly popular in Western countries. We investigated the effects of Lycium Chinense on acid sphingomyelinase and sphingomyelin species in relation to gene expression. METHODS: We prepared Lycium Chinense berry extracts and evaluated their antioxidant properties. Increasing amount of extracts was used to test cytotoxic and genotoxic effect on HepG2 cells. Gene expression, protein amount and enzyme activity of acid sphingomyelinase were tested by RT-PCR, immunoblotting and enzymatic activity assay, respectively. Sphingomyelin species were analyzed by UFLC MS/MS. A panel of 96 genes involved in oxidative stress, proliferation, apoptosis and cancer was used to test the effect of LC on gene expression. GLRX2, RNF7, and PTGS1 proteins were analyzed by immunoblotting. RESULTS: We showed that Lycium Chinense berries have high antioxidant properties, have an IC50value of 9.55 mg/mL, do not induce genotoxic effect and maintain high level of cell viability. The berry extracts inhibit acid sphingomyelinase activity and increase both very long fatty acid sphingomyelin species and unsaturated fatty acid sphingomyelin species. Among 96 genes, Lycium Chinense berries up-regulate Glutaredoxin 2 and Ring Finger Protein 7 genes and proteins, able to protect cells from apoptosis. Intrigantly, Lycium Chinense berries down-regulates Prostaglandin H synthase 1 gene but the protein is not expressed in HepG2 cells. CONCLUSION: The results identify acid sphingomyelinase as a novel target of Lycium Chinense berries to decrease saturated/unsaturated fatty acid sphingomyelin ratio, known to be useful for cell health. Consistent with these data, the berries regulate specifically gene expression to protect cells from apoptosis.


Asunto(s)
Supervivencia Celular/efectos de los fármacos , Esfingomielina Fosfodiesterasa/biosíntesis , Esfingomielinas/metabolismo , Antioxidantes/administración & dosificación , Antioxidantes/química , Frutas/química , Regulación de la Expresión Génica/efectos de los fármacos , Células Hep G2 , Humanos , Lycium/química , Medicina Tradicional China , Extractos Vegetales/administración & dosificación , Extractos Vegetales/química
16.
Int J Mol Sci ; 16(2): 2307-19, 2015 Jan 22.
Artículo en Inglés | MEDLINE | ID: mdl-25622250

RESUMEN

The use of gentamicin for the treatment of bacterial infection has always been an interesting and highly speculated issue for the scientific community. Conversely, its effect on cancer cells has been very little investigated. We studied the effect of high doses of gentamicin on non-Hodgkin's T-cell human lymphoblastic lymphoma (SUP-T1). We showed that gentamicin delayed cell growth and induced cell death in lymphoma cells with a rather mild effect on lymphocytes. In SUP-T1 cells, GAPDH, B2M, CDKN1A and CDKN1B were down-expressed in comparison with lymphocytes. Gentamicin treatment in SUP-T1 cells restored the expression of GAPDH, B2M and CDKN1A to values similar to those of lymphocytes and caused overexpression of CDKN1B. The drug acted via sphingomyelin metabolism; in whole cells, sphingomyelinase activity was stimulated, whereas in purified nuclei, sphingomyelinase activity was inhibited and that of sphingomyelin-synthase was stimulated, with a consequent high level of nuclear sphingomyelin content. We suggest that the increase of nuclear sphingomyelin might enrich the nucleus of lipid microdomains that act as a platform for active chromatin and, thus, might be responsible for gene expression. It is possible that in lymphoblastic lymphoma, high doses of gentamicin induce a beneficial therapeutic outcome.


Asunto(s)
Antibacterianos/toxicidad , Núcleo Celular/metabolismo , Proliferación Celular/efectos de los fármacos , Gentamicinas/toxicidad , Esfingomielinas/metabolismo , Línea Celular Tumoral , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/genética , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/metabolismo , Inhibidor p27 de las Quinasas Dependientes de la Ciclina/genética , Inhibidor p27 de las Quinasas Dependientes de la Ciclina/metabolismo , Regulación hacia Abajo/efectos de los fármacos , Gliceraldehído-3-Fosfato Deshidrogenasas/genética , Gliceraldehído-3-Fosfato Deshidrogenasas/metabolismo , Humanos , Metabolismo de los Lípidos/efectos de los fármacos , Esfingomielina Fosfodiesterasa/metabolismo
17.
Int J Mol Sci ; 15(7): 11555-65, 2014 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-24979136

RESUMEN

Proliferating thyroid cells are more sensitive to UV-C radiations than quiescent cells. The effect is mediated by nuclear phosphatidylcholine and sphingomyelin metabolism. It was demonstrated that proton beams arrest cell growth and stimulate apoptosis but until now there have been no indications in the literature about their possible mechanism of action. Here we studied the effect of protons on FRTL-5 cells in culture. We showed that proton beams stimulate slightly nuclear neutral sphingomyelinase activity and inhibit nuclear sphingomyelin-synthase activity in quiescent cells whereas stimulate strongly nuclear neutral sphingomyelinase activity and do not change nuclear sphingomyelin-synthase activity in proliferating cells. The study of neutral sphingomyelinase/sphingomyelin-synthase ratio, a marker of functional state of the cells, indicated that proton beams induce FRTL-5 cells in a proapoptotic state if the cells are quiescent and in an initial apoptotic state if the cells are proliferating. The changes of cell life are accompanied by a decrease of nuclear sphingomyelin and increase of bax protein.


Asunto(s)
Protones , Esfingomielina Fosfodiesterasa/metabolismo , Animales , Apoptosis , Línea Celular , Células Epiteliales/metabolismo , Células Epiteliales/efectos de la radiación , Ratas , Glándula Tiroides/citología , Transferasas (Grupos de Otros Fosfatos Sustitutos)/metabolismo , Proteína X Asociada a bcl-2/genética , Proteína X Asociada a bcl-2/metabolismo
18.
Int J Mol Sci ; 15(11): 19832-46, 2014 Oct 31.
Artículo en Inglés | MEDLINE | ID: mdl-25365174

RESUMEN

The action of dexamethasone is initiated by, and strictly dependent upon, the interaction of the drug with its receptor followed by its translocation into the nucleus where modulates gene expression. Where the drug localizes at the intranuclear level is not yet known. We aimed to study the localization of the drug in nuclear lipid microdomains rich in sphingomyelin content that anchor active chromatin and act as platform for transcription modulation. The study was performed in non-Hodgkin's T cell human lymphoblastic lymphoma (SUP-T1 cell line). We found that when dexamethasone enters into the nucleus it localizes in nuclear lipid microdomains where influences sphingomyelin metabolism. This is followed after 24 h by a cell cycle block accompanied by the up-regulation of cyclin-dependent kinase inhibitor 1A (CDKN1A), cyclin-dependent kinase inhibitor 1B (CDKN1B), growth arrest and DNA-damage 45A (GADD45A), and glyceraldehyde 3-phosphate dehydrogenase (GAPDH) genes and by the reduction of signal transducer and activator of transcription 3 (STAT3) and phospho signal transducer and activator of transcription 3 (phoshoSTAT3) proteins. After 48 h some cells show morphological changes characteristic of apoptosis while the number of the cells that undergo cell division and express B-cell lymphoma-2 (Bcl-2) is very low. We suggest that the integrity of nuclear lipid microdomains is important for the response to glucocorticoids of cancer cells.


Asunto(s)
Núcleo Celular/metabolismo , Proliferación Celular/efectos de los fármacos , Dexametasona/farmacología , Microdominios de Membrana/metabolismo , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Línea Celular Tumoral , Cromatina/metabolismo , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/genética , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/metabolismo , Inhibidor p27 de las Quinasas Dependientes de la Ciclina/genética , Inhibidor p27 de las Quinasas Dependientes de la Ciclina/metabolismo , Gliceraldehído 3-Fosfato Deshidrogenasa (NADP+)/genética , Gliceraldehído 3-Fosfato Deshidrogenasa (NADP+)/metabolismo , Humanos , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Factor de Transcripción STAT3/metabolismo , Esfingomielina Fosfodiesterasa/metabolismo , Esfingomielinas/metabolismo , Transferasas (Grupos de Otros Fosfatos Sustitutos)/metabolismo , Regulación hacia Arriba/efectos de los fármacos
19.
Int J Mol Sci ; 14(4): 6529-41, 2013 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-23528885

RESUMEN

Nuclear sphingomyelin is a key molecule for cell proliferation. This molecule is organized with cholesterol and proteins to form specific lipid microdomains bound to the inner nuclear membrane where RNA is synthesized. Here, we have reported the ability of the sphingomyelin present in the nuclear microdomain to bind DNA and regulate its synthesis, and to highlight its role in cell proliferation induced by partial hepatectomy. During G1/S transition of the cell cycle, sphingomyelin and DNA content is very high and it is strongly reduced after exogenous sphingomyelinase treatment. During the S-phase of the cell cycle, the stimulation of sphingomyelinase and inhibition of sphingomyelin-synthase are accompanied by the DNA synthesis start. To assess the specificity of the results, experiments were repeated with trifluoperazine, a drug known to affect the synthesis of lipids and DNA and to stimulate sphingomyelinase activity. The activity of sphingomyelinase is stimulated in the first hour after hepatectomy and sphingomyelin-DNA synthesis is strongly attenuated. It may be hypothesized that the nuclear microdomain represents a specific area of the inner nuclear membrane that acts as an active site of chromatin anchorage thanks to the stabilizing action of sphingomyelin. Thus, sphingomyelin metabolism in nuclear lipid microdomains is suggested to regulate cell proliferation.


Asunto(s)
Núcleo Celular/metabolismo , ADN/metabolismo , Regeneración Hepática , Microdominios de Membrana/metabolismo , Esfingomielinas/metabolismo , Animales , Núcleo Celular/efectos de los fármacos , ADN/biosíntesis , Femenino , Regeneración Hepática/efectos de los fármacos , Microsomas Hepáticos/efectos de los fármacos , Microsomas Hepáticos/metabolismo , Fosfolípidos/metabolismo , ARN/metabolismo , Ratas Sprague-Dawley , Fracciones Subcelulares/metabolismo , Trifluoperazina/farmacología
20.
Materials (Basel) ; 14(22)2021 Nov 11.
Artículo en Inglés | MEDLINE | ID: mdl-34832198

RESUMEN

Heterogeneous catalysts are progressively expanding their field of application, from high-throughput reactions for traditional industrial chemistry with production volumes reaching millions of tons per year, a sector in which they are key players, to more niche applications for the production of fine chemicals. These novel applications require a progressive utilization reduction of fossil feedstocks, in favor of renewable ones. Biomasses are the most accessible source of organic precursors, having as advantage their low cost and even distribution across the globe. Unfortunately, they are intrinsically inhomogeneous in nature and their efficient exploitation requires novel catalysts. In this process, an accurate design of the active phase performing the reaction is important; nevertheless, we are often neglecting the importance of the support in guaranteeing stable performances and improving catalytic activity. This review has the goal of gathering and highlighting the cases in which the supports (either derived or not from biomass wastes) share the worth of performing the catalysis with the active phase, for those reactions involving the synthesis of fine chemicals starting from biomasses as feedstocks.

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