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1.
Int J Biol Macromol ; 271(Pt 2): 132456, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38777013

RESUMO

In this study, the stabilization mechanism and digestion behavior of Pickering emulsion prepared by a combination of chitosan (CS) and TEMPO-oxidized hyaluronic acid (HA) were investigated. Conductometric titration was used to determine the degree of oxidation and carboxylate content of TEMPO-oxidized HA. The results showed that the degree of oxidation increased proportionally with increasing oxidation time, and the electrostatic and hydrogen bonding interactions with CS were significantly enhanced. The results of FTIR and TEM showed the formation of CS/oxidized HA nanoparticles (CS/oxidized-HANPs). In addition, the contact angle of CS/oxidized-HANPs is closed to 77°, thereby providing higher desorption energy at the interface. Rheological results showed that the Pickering emulsion exhibited a gel-like network structure and higher viscosity. In vitro digestion results suggested that the quercetin (Que) bioaccessibility of the CS/oxidation HANps-stabilized Pickering emulsion with an oxidation time of 20 min was better than that of the conventional emulsion prepared with CS alone. The research is expected to develop novel polysaccharide-based Pickering emulsion delivery systems for functional compounds.


Assuntos
Quitosana , Óxidos N-Cíclicos , Emulsões , Ácido Hialurônico , Nanopartículas , Oxirredução , Quitosana/química , Ácido Hialurônico/química , Emulsões/química , Nanopartículas/química , Óxidos N-Cíclicos/química , Viscosidade , Reologia , Quercetina/química
2.
Life Sci ; 336: 122291, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38030060

RESUMO

AIMS: Sepsis represents a profound proinflammatory response with a major contribution from oxidative injury. Here we evaluated possible impact of heavy metal scavenger metallothionein (MT) on endotoxin lipopolysaccharide (LPS)-induced oxidative stress, endoplasmic reticulum (ER) stress, autophagy, and ferroptosis enroute to myocardial injury along with interplay among these stress domains. MATERIALS AND METHODS: Echocardiographic, cardiomyocyte mechanical and intracellular Ca2+ responses were monitored in myocardia from WT and transgenic mice with cardiac-selective MT overexpression challenged with LPS. Oxidative stress, stress signaling (p38, ERK, JNK), ER stress, autophagy, and ferroptosis were scrutinized. KEY FINDINGS: RNAseq analysis revealed discrepant patterns in ferroptosis between LPS-exposed and normal murine hearts. LPS insult enlarged LV end systolic dimension, suppressed fractional shortening, ejection fraction, maximal velocity of shortening/relengthening and peak shortening, as well as elongated relengthening along with dampened intracellular Ca2+ release and reuptake. In addition, LPS triggered oxidative stress (lowered glutathione/glutathione disulfide ratio and O2- production), activation of stress cascades (p38, ERK, JNK), ER stress (GRP78, PERK, Gadd153, and IRE1α), inflammation (TNFα and iNOS), unchecked autophagy (LCB3, Beclin-1 and Atg7), ferroptosis (GPx4 and SLC7A11) and interstitial fibrosis. Although MT overexpression itself did not reveal response on cardiac function, it attenuated or mitigated LPS-evoked alterations in echocardiographic, cardiomyocyte contractile and intracellular Ca2+ characteristics, O2- production, TNFα level, ER stress and ferroptosis (without affecting autophagy, elevated AMP/ATP ratio, and iNOS). In vitro evidence revealed beneficial effects of suppression of oxidative stress, ER stress and ferroptosis against LPS-elicited myocardial anomalies. SIGNIFICANCE: These data strongly support the therapeutic promises of MT and ferroptosis in septic cardiomyopathy.


Assuntos
Ferroptose , Cardiopatias Congênitas , Sepse , Camundongos , Animais , Lipopolissacarídeos/toxicidade , Metalotioneína , Endorribonucleases , Fator de Necrose Tumoral alfa/farmacologia , Proteínas Serina-Treonina Quinases , Miócitos Cardíacos , Camundongos Transgênicos , Autofagia , Estresse do Retículo Endoplasmático , Sepse/complicações , Contração Miocárdica
3.
Nat Commun ; 12(1): 1174, 2021 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-33608552

RESUMO

Adult hippocampal neurogenesis contributes to learning and memory, and is sensitive to a variety of environmental stimuli. Exposure to a hypomagnetic field (HMF) influences the cognitive processes of various animals, from insects to human beings. However, whether HMF exposure affect adult hippocampal neurogenesis and hippocampus-dependent cognitions is still an enigma. Here, we showed that male C57BL/6 J mice exposed to HMF by means of near elimination of the geomagnetic field (GMF) exhibit significant impairments of adult hippocampal neurogenesis and hippocampus-dependent learning, which is strongly correlated with a reduction in the content of reactive oxygen species (ROS). However, these deficits seen in HMF-exposed mice could be rescued either by elevating ROS levels through pharmacological inhibition of ROS removal or by returning them back to GMF. Therefore, our results suggest that GMF plays an important role in adult hippocampal neurogenesis through maintaining appropriate endogenous ROS levels.


Assuntos
Cognição/fisiologia , Cognição/efeitos da radiação , Hipocampo/patologia , Hipocampo/efeitos da radiação , Campos Magnéticos/efeitos adversos , Neurogênese/fisiologia , Neurogênese/efeitos da radiação , Adulto , Animais , Proliferação de Células , Regulação da Expressão Gênica no Desenvolvimento , Humanos , Aprendizagem , Masculino , Memória , Camundongos , Camundongos Endogâmicos C57BL , Células-Tronco Neurais , Neurogênese/genética , Espécies Reativas de Oxigênio
4.
Bioelectromagnetics ; 41(8): 573-580, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32997824

RESUMO

Organisms, including humans, could be exposed to hypomagnetic fields (HMFs, intensity <5 µT), e.g. in some artificially shielded magnetic environments and during deep-space flights. Previous studies have demonstrated that HMF exposure could have negative effects on the central nervous system and embryonic development in many animals. However, the underlying mechanisms remain unknown. Studies have revealed that HMFs affect cellular reactive oxygen species (ROS) levels and thereby alter physiological and biological processes in organisms. ROS, the major component of highly active free radicals, which are ubiquitous in biological systems, were hypothesized to be the candidate signaling molecules that regulate diverse physiological processes in response to changes in magnetic fields. Here, we summarize the recent advances in the study of HMF-induced negative effects on the central nervous system and early embryonic development in animals, focusing on cellular ROS and their role in response to HMFs. Furthermore, we discuss the potential mechanism through which HMFs regulate ROS levels in cells. © 2020 Bioelectromagnetics Society.


Assuntos
Campos Magnéticos , Espécies Reativas de Oxigênio/metabolismo , Animais , Humanos
5.
Artigo em Inglês | MEDLINE | ID: mdl-31227860

RESUMO

Previously, two studies have provided evidence that bats can use magnetic field cues for homing or roosting. For insectivorous bats, it is well established that foraging represents one of the most fundamental behaviors in animals relies on their ability to echolocate. Whether echolocating bats can also use magnetic cues during foraging remains unknown, however. Here, we tested the orientation behavior of Chinese noctules (Nyctalus plancyi) during foraging in a plus-shaped, 4-channel apparatus under different magnetic field conditions. To minimize the effects of spatial memory on orientation from repeated experiments, naïve bats were tested only once in each experimental condition. As expected, under geomagnetic field and a food resource offered conditions, the bats significantly preferred to enter the channel containing food, indicating that they primarily relied on direct sensory signals unrelated to magnetic cues. In contrast, when we offered food simultaneously in all four channels and minimized any differences in all other sensory signals available, the bats exhibited a clear directional preference to forage along the magnetic field direction under either geomagnetic field or a magnetic field in which the horizontal component was rotated by 90°. Our study offers a novel evidence for the importance of a geomagnetic field during foraging.


Assuntos
Comportamento Animal/fisiologia , Quirópteros/fisiologia , Campos Magnéticos , Orientação Espacial/fisiologia , Animais , Sinais (Psicologia)
6.
Genome Announc ; 4(5)2016 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-27795283

RESUMO

The magnetotactic bacterium Magnetospirillum sp. strain XM-1 was recently isolated from the Xi'an City moat, China. It belongs to the Rhodospirillaceae family in the Alphaproteobacteria class. Here, we report the complete genome sequence of XM-1. The genome contains a single circular chromosome of 4,825,187 bp and a plasmid of 167,290 bp.

8.
Guang Pu Xue Yu Guang Pu Fen Xi ; 35(5): 1233-8, 2015 May.
Artigo em Chinês | MEDLINE | ID: mdl-26415434

RESUMO

The whole spectrum usually contains a lot of redundant information in the near-infrared spectroscopy model, the presence of redundant information will increase the model resolution time and increase the difficulty of parsing model, Therefore, how to select the characteristic wavelength quickly and effectly is very crucial. In this paper, we combined the algorithm based on SPA (successive projections algorithm ) with IPLS (interval partial least squares ) to selec the characteristic wavelength in the fermentation of wheat straw microbial biomass, A total of 85 samples prepared by measuring microbial biomass using glucosamine method, 68 samples are chosen as calibration set and 17 simples are chosen as verification set. First, the whole spectral region 520 points are segmented modeling according to the interval wavelength point size 10, 20, 30, 40 and 4 450~4 925 cm-1, 9 194~9 993 cm-1 two-band range are selected as the characteristic wavelength band, then pick out the new feature wavelength points by Successive Projections Algorithm band and Genetic Algorithm (GA), comprehensive analysis and comparison the result of model. The experimental results show that the using of IPLS-SPA algorithm to select the combination band 4 450~4 925 cm-1 & 9 194~9 993 cm-1 has the best modeling effect, compared with the modeling of whole spectrum, the wavelength points decrease from 520 to 10, the correction coefficient of determination R2 rised from 0. 884 9 to 0. 945 28, root mean square error (RMSE) dropped from 11. 104 9 to 8. 203 3, although the genetic algorithm model achieved the better accuracy, but the results are instable and have a strong randomness , while IPLS combined SPA method can select characteristic wavelength information stability and accurately, which can improve the model calculation speed and reduce the fitting difficulty of the model, it can be used as a new reference method for band selection. The results show that using near infrared spectroscopy method for straw biomass rapid detection is feasible.


Assuntos
Biomassa , Espectroscopia de Luz Próxima ao Infravermelho , Algoritmos , Fermentação , Análise dos Mínimos Quadrados , Modelos Teóricos , Caules de Planta , Triticum
9.
PLoS One ; 10(4): e0123205, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25922944

RESUMO

How animals, including mammals, can respond to and utilize the direction and intensity of the Earth's magnetic field for orientation and navigation is contentious. In this study, we experimentally tested whether the Chinese Noctule, Nyctalus plancyi (Vespertilionidae) can sense magnetic field strengths that were even lower than those of the present-day geomagnetic field. Such field strengths occurred during geomagnetic excursions or polarity reversals and thus may have played an important role in the evolution of a magnetic sense. We found that in a present-day local geomagnetic field, the bats showed a clear preference for positioning themselves at the magnetic north. As the field intensity decreased to only 1/5th of the natural intensity (i.e., 10 µT; the lowest field strength tested here), the bats still responded by positioning themselves at the magnetic north. When the field polarity was artificially reversed, the bats still preferred the new magnetic north, even at the lowest field strength tested (10 µT), despite the fact that the artificial field orientation was opposite to the natural geomagnetic field (P<0.05). Hence, N. plancyi is able to detect the direction of a magnetic field even at 1/5th of the present-day field strength. This high sensitivity to magnetic fields may explain how magnetic orientation could have evolved in bats even as the Earth's magnetic field strength varied and the polarity reversed tens of times over the past fifty million years.


Assuntos
Quirópteros/fisiologia , Campos Magnéticos , Orientação , Animais , Comportamento Animal , Planeta Terra , Masculino
10.
Guang Pu Xue Yu Guang Pu Fen Xi ; 34(2): 350-3, 2014 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-24822399

RESUMO

In order to explore a simple, rapid and efficient tomato quality detection method, in the present experiment near infrared spectroscopy and optical fiber sensing technology were applied to quickly measure the nutrition ingredient content in tomato juice samples. The main instrument used in this experiment was near infrared optical fiber spectrometer in a wavelength range from 900 to 2 500 nm, which measured the absorbance of the tomato juice samples; A collection of one hundred and sixty-four tomato juice samples were selected as the standard samples, the spectra and the corresponding chemical value were measured. Partial least squares (PLS) was adopted to establish the mathematical model of the total acid and soluble sugar content in tomato juice samples, and the regression equation was statistically analysed. The total acid in tomato juice prediction correlation coefficient was 0.967, calibration standard deviation (RMSEC) was 0.133, standard error of prediction (RMSEP) was 0.103; the soluble sugar prediction correlation coefficient is 0.976, calibration standard deviation (RMSEC) was 0.463, and the standard error of prediction (RMSEP) was 0. 460. The above data achieved better forecasting results, which showed that the method of quantitative analysis of tomato fruit multicomponent content was feasible. The method is rapid, simple and can do multicomponent analysis on the same sample simultaneously. It is a promising sensor and gradually becoming a international research focus in sensor field.


Assuntos
Ácidos/química , Bebidas/análise , Carboidratos/química , Frutas/química , Solanum lycopersicum/química , Calibragem , Análise dos Mínimos Quadrados , Fibras Ópticas , Espectroscopia de Luz Próxima ao Infravermelho
11.
Guang Pu Xue Yu Guang Pu Fen Xi ; 34(10): 2723-7, 2014 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-25739215

RESUMO

In the present study, a new method using near infrared spectroscopy combined with optical fiber sensing technology was applied to the analysis of hogwash oil in blended oil. The 50 samples were a blend of frying oil and "nine three" soybean oil according to a certain volume ratio. The near infrared transmission spectroscopies were collected and the quantitative analysis model of frying oil was established by partial least squares (PLS) and BP artificial neural network The coefficients of determina- tion of calibration sets were 0.908 and 0.934 respectively. The coefficients of determination of validation sets were 0.961 and 0.952, the root mean square error of calibrations (RMSEC) was 0.184 and 0.136, and the root mean square error of predictions (RMSEP) was all 0.111 6. They conform to the model application requirement. At the same time, frying oil and qualified edible oil were identified with the principal component analysis (PCA), and the accurate rate was 100%. The experiment proved that near infrared spectral technology not only can quickly and accurately identify hogwash oil, but also can quantitatively detect hog- wash oil. This method has a wide application prospect in the detection of oil.


Assuntos
Contaminação de Alimentos , Óleos de Plantas/análise , Espectroscopia de Luz Próxima ao Infravermelho , Calibragem , Análise dos Mínimos Quadrados , Fibras Ópticas , Análise de Componente Principal , Óleo de Soja/análise
12.
Biochim Biophys Acta ; 1832(4): 574-84, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23354068

RESUMO

ER stress triggers myocardial contractile dysfunction while effective therapeutic regimen is still lacking. Mitochondrial aldehyde dehydrogenase (ALDH2), an essential mitochondrial enzyme governing mitochondrial and cardiac function, displays distinct beneficial effect on the heart. This study was designed to evaluate the effect of ALDH2 on ER stress-induced cardiac anomalies and the underlying mechanism involved with a special focus on autophagy. WT and ALDH2 transgenic mice were subjected to the ER stress inducer thapsigargin (1mg/kg, i.p., 48h). Echocardiographic, cardiomyocyte contractile and intracellular Ca(2+) properties as well as myocardial histology, autophagy and autophagy regulatory proteins were evaluated. ER stress led to compromised echocardiographic indices (elevated LVESD, reduced fractional shortening and cardiac output), cardiomyocyte contractile and intracellular Ca(2+) properties and cell survival, associated with upregulated autophagy, dampened phosphorylation of Akt and its downstream signal molecules TSC2 and mTOR, the effects of which were alleviated or mitigated by ALDH2. Thapsigargin promoted ER stress proteins Gadd153 and GRP78 without altering cardiomyocyte size and interstitial fibrosis, the effects of which were unaffected by ALDH2. Treatment with thapsigargin in vitro mimicked in vivo ER stress-induced cardiomyocyte contractile anomalies including depressed peak shortening and maximal velocity of shortening/relengthening as well as prolonged relengthening duration, the effect of which was abrogated by the autophagy inhibitor 3-methyladenine and the ALDH2 activator Alda-1. Interestingly, Alda-1-induced beneficial effect against ER stress was obliterated by autophagy inducer rapamycin, Akt inhibitor AktI and mTOR inhibitor RAD001. These data suggest a beneficial role of ALDH2 against ER stress-induced cardiac anomalies possibly through autophagy reduction.


Assuntos
Aldeído Desidrogenase , Autofagia , Retículo Endoplasmático , Contração Miocárdica/genética , Adenina/análogos & derivados , Adenina/farmacologia , Aldeído Desidrogenase/genética , Aldeído Desidrogenase/metabolismo , Aldeído-Desidrogenase Mitocondrial , Animais , Arritmias Cardíacas/metabolismo , Arritmias Cardíacas/patologia , Síndrome de Brugada , Cálcio/metabolismo , Doença do Sistema de Condução Cardíaco , Retículo Endoplasmático/genética , Retículo Endoplasmático/metabolismo , Chaperona BiP do Retículo Endoplasmático , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Sistema de Condução Cardíaco/anormalidades , Sistema de Condução Cardíaco/metabolismo , Sistema de Condução Cardíaco/patologia , Humanos , Camundongos , Camundongos Transgênicos , Mitocôndrias/genética , Mitocôndrias/metabolismo , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Serina-Treonina Quinases TOR/antagonistas & inibidores , Serina-Treonina Quinases TOR/metabolismo , Proteína 2 do Complexo Esclerose Tuberosa , Proteínas Supressoras de Tumor/antagonistas & inibidores , Proteínas Supressoras de Tumor/metabolismo
13.
Cell Immunol ; 278(1-2): 84-90, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23121979

RESUMO

Microglia participates in the regulation of many inflammation-related pathological processes in the central nervous system, but how microglial activation is regulated has not been fully understood. Here, by using a microglial cell line, we show that microglia, like other macrophages, are activated by inflammatory stimuli in a polarized manner. The LPS-polarized M1 microglia appeared to be unable to respond to a secondary IL4 stimulation, while IL4-polarized M2 microglia could respond to secondary LPS stimulation. We also show that Notch signaling is involved in microglial polarization. When Notch signaling was blocked, the M1 polarization was suppressed, while the M2 polarization was promoted. Withdraw of the Notch signal inhibitor did not permit M2 N9 cells to re-polarize to M1 upon LPS stimulation, suggesting that the effects of Notch blockade on microglial polarization could be "memorized" by cells. These results suggest complicated mechanisms including epigenetic programs in the regulation of macrophage polarization.


Assuntos
Interleucina-4/farmacologia , Lipopolissacarídeos/farmacologia , Microglia/efeitos dos fármacos , Receptores Notch/imunologia , Secretases da Proteína Precursora do Amiloide/antagonistas & inibidores , Animais , Linhagem Celular , Epigênese Genética , Camundongos , Microglia/citologia , Microglia/imunologia , Óxido Nítrico/biossíntese , Óxido Nítrico/imunologia , Receptores Notch/antagonistas & inibidores , Receptores Notch/genética , Transdução de Sinais
14.
Free Radic Biol Med ; 49(7): 1238-53, 2010 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-20678571

RESUMO

Chronic alcohol intake leads to the development of alcoholic cardiomyopathy manifested by cardiac hypertrophy and contractile dysfunction. This study was designed to examine the effects of transgenic overexpression of insulin-like growth factor 1 (IGF-1) on alcohol-induced cardiac contractile dysfunction. Wild-type FVB and cardiac-specific IGF-1 mice were placed on a 4% alcohol or control diet for 16weeks. Cardiac geometry and mechanical function were evaluated by echocardiography and cardiomyocyte and intracellular Ca(2+) properties. Histological analyses for cardiac fibrosis and apoptosis were evaluated by Masson trichrome staining and TUNEL assay, respectively. Expression and phosphorylation of Cu/Zn superoxide dismutase (SOD1), Ca(2+) handling proteins, and key signaling molecules for survival including Akt, mTOR, GSK3beta, Foxo3a, and the negative regulator of Akt, phosphatase and tensin homolog on chromosome 10 (PTEN), as well as mitochondrial proteins UCP-2 and PGC1alpha, were evaluated by Western blot analysis. Chronic alcohol intake led to cardiac hypertrophy, interstitial fibrosis, reduced mitochondrial number, compromised cardiac contractile function and intracellular Ca(2+) handling, decreased SOD1 expression, elevated superoxide production, and overt apoptosis, all of which, with the exception of cardiac hypertrophy, were abrogated by the IGF-1 transgene. Immunoblotting data showed reduced phosphorylation of Akt, mTOR, GSK3beta, and Foxo3a; upregulated Foxo3a and PTEN; and dampened SERCA2a, PGC1alpha, and UCP-2 after alcohol intake. All these alcohol-induced changes in survival and mitochondrial proteins were alleviated by IGF-1. Taken together, these data favor a beneficial role for IGF-1 in alcohol-induced myocardial contractile dysfunction independent of cardiac hypertrophy.


Assuntos
Cardiomiopatia Alcoólica/metabolismo , Etanol/administração & dosagem , Coração/efeitos dos fármacos , Fator de Crescimento Insulin-Like I/metabolismo , Miocárdio , Animais , Apoptose/efeitos dos fármacos , Apoptose/genética , Cardiomiopatia Alcoólica/genética , Cardiomiopatia Alcoólica/patologia , Cardiomiopatia Alcoólica/fisiopatologia , Quinase 3 da Glicogênio Sintase/metabolismo , Glicogênio Sintase Quinase 3 beta , Coração/anatomia & histologia , Coração/fisiologia , Hipertrofia , Fator de Crescimento Insulin-Like I/genética , Camundongos , Camundongos Transgênicos , Contração Miocárdica/efeitos dos fármacos , Contração Miocárdica/genética , Miocárdio/metabolismo , Miocárdio/patologia , Especificidade de Órgãos , PTEN Fosfo-Hidrolase/biossíntese , PTEN Fosfo-Hidrolase/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Superóxido Dismutase/biossíntese , Superóxido Dismutase/genética , Superóxido Dismutase-1 , Serina-Treonina Quinases TOR/metabolismo , Transgenes/genética
15.
Mol Cell Biochem ; 340(1-2): 7-14, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20157766

RESUMO

The Notch signaling pathway has been implicated in the development of several leukemia and lymphoma. In order to investigate the relationship between Notch signaling and acute myeloid leukemia (AML), in this study, we expressed a recombinant Notch ligand protein, the DSL domain of the human Jagged1 fused with GST (GST-Jag1). GST-Jag1 could activate Notch signaling in the human promyelocytic leukemia cell line HL60, as shown by a reporter assay and the induced expression of Notch effector gene Hes1 and Hes5. However, GST-Jag1 had no effect on the proliferation and survival of HL60 cells. HL60 cells expressed both Notch ligands and receptors, and had a potential of reciprocal stimulation of Notch signaling between cells. We, therefore, blocked Notch signaling in cultured HL60 cells using a gamma-secretase inhibitor (GSI). We found that GSI inhibited the proliferation of HL60 cells significantly by blocking the cell-cycle progression in the G1 phase. Furthermore, GSI induced remarkably apoptosis of HL60 cells. These changes in GSI-treated HL60 cells correlated with the down-regulation of c-Myc and Bcl2, and the low phosphorylation of the Rb protein. These results suggested that reciprocal Notch signaling might be necessary for the proliferation and survival of AML cells, possibly through the maintenance of the expression of c-Myc and Bcl2, as well as the phosphorylation of the Rb protein.


Assuntos
Proliferação de Células , Leucemia Promielocítica Aguda/metabolismo , Receptores Notch/metabolismo , Proteína do Retinoblastoma/metabolismo , Transdução de Sinais , Secretases da Proteína Precursora do Amiloide/antagonistas & inibidores , Secretases da Proteína Precursora do Amiloide/metabolismo , Apoptose , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Proteínas de Ligação ao Cálcio/metabolismo , Ciclo Celular , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/farmacologia , Células HL-60 , Células HeLa , Proteínas de Homeodomínio/metabolismo , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Proteína Jagged-1 , Leucemia Promielocítica Aguda/genética , Leucemia Promielocítica Aguda/patologia , Proteínas de Membrana/metabolismo , Fosforilação , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteínas Proto-Oncogênicas c-myc/metabolismo , Proteínas Recombinantes de Fusão/metabolismo , Proteínas Repressoras/metabolismo , Proteínas Serrate-Jagged , Transdução de Sinais/efeitos dos fármacos , Fatores de Tempo , Fatores de Transcrição HES-1 , Transfecção
16.
J Mol Cell Cardiol ; 48(2): 367-78, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19914257

RESUMO

Sepsis is characterized by systematic inflammation where oxidative damage plays a key role in organ failure. This study was designed to examine the impact of the antioxidant metallothionein (MT) on lipopolysaccharide (LPS)-induced cardiac contractile and intracellular Ca(2+) dysfunction, oxidative stress, endoplasmic reticulum (ER) stress and autophagy. Mechanical and intracellular Ca(2+) properties were examined in hearts from FVB and cardiac-specific MT overexpression mice treated with LPS. Oxidative stress, activation of mitogen-activated protein kinase pathways (ERK, JNK and p38), ER stress, autophagy and inflammatory markers iNOS and TNFalpha were evaluated. Our data revealed enlarged end systolic diameter, decreased fractional shortening, myocyte peak shortening and maximal velocity of shortening/relengthening as well as prolonged duration of relengthening in LPS-treated FVB mice associated with reduced intracellular Ca(2+) release and decay. LPS treatment promoted oxidative stress (reduced glutathione/glutathione disulfide ratio and ROS generation). Western blot analysis revealed greater iNOS and TNFalpha, activation of ERK, JNK and p38, upregulation of ER stress markers GRP78, Gadd153, PERK and IRE1alpha, as well as the autophagy markers Beclin-1, LCB3 and Atg7 in LPS-treated mouse hearts without any change in total ERK, JNK and p38. Interestingly, these LPS-induced changes in echocardiographic, cardiomyocyte mechanical and intracellular Ca(2+) properties, ROS, stress signaling and ER stress (but not autophagy, iNOS and TNFalpha) were ablated by MT. Antioxidant N-acetylcysteine and the ER stress inhibitor tauroursodeoxycholic acid reversed LPS-elicited depression in cardiomyocyte contractile function. LPS activated AMPK and its downstream signaling ACC in conjunction with an elevated AMP/ATP ratio, which was unaffected by MT. Taken together, our data favor a beneficial effect of MT in the management of cardiac dysfunction in sepsis.


Assuntos
Autofagia , Retículo Endoplasmático/patologia , Metalotioneína/metabolismo , Contração Miocárdica/fisiologia , Miocárdio/patologia , Estresse Oxidativo , Sepse/fisiopatologia , Adenilato Quinase/metabolismo , Animais , Autofagia/efeitos dos fármacos , Fenômenos Biomecânicos/efeitos dos fármacos , Cálcio/metabolismo , Retículo Endoplasmático/efeitos dos fármacos , Chaperona BiP do Retículo Endoplasmático , Ativação Enzimática/efeitos dos fármacos , Comportamento Alimentar/efeitos dos fármacos , Inflamação/complicações , Membranas Intracelulares/efeitos dos fármacos , Membranas Intracelulares/metabolismo , Espaço Intracelular/efeitos dos fármacos , Espaço Intracelular/metabolismo , Dose Letal Mediana , Lipopolissacarídeos/farmacologia , Lisossomos/efeitos dos fármacos , Lisossomos/metabolismo , Camundongos , Contração Miocárdica/efeitos dos fármacos , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/enzimologia , Miócitos Cardíacos/patologia , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Sepse/complicações , Sepse/patologia , Transdução de Sinais/efeitos dos fármacos
17.
PLoS One ; 4(10): e7572, 2009 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-19859544

RESUMO

Bone marrow (BM)-derived endothelial progenitor cells (EPC) have therapeutic potentials in promoting tissue regeneration, but how these cells are modulated in vivo has been elusive. Here, we report that RBP-J, the critical transcription factor mediating Notch signaling, modulates EPC through CXCR4. In a mouse partial hepatectomy (PHx) model, RBP-J deficient EPC showed attenuated capacities of homing and facilitating liver regeneration. In resting mice, the conditional deletion of RBP-J led to a decrease of BM EPC, with a concomitant increase of EPC in the peripheral blood. This was accompanied by a down-regulation of CXCR4 on EPC in BM, although CXCR4 expression on EPC in the circulation was up-regulated in the absence of RBP-J. PHx in RBP-J deficient mice induced stronger EPC mobilization. In vitro, RBP-J deficient EPC showed lowered capacities of adhering, migrating, and forming vessel-like structures in three-dimensional cultures. Over-expression of CXCR4 could at least rescue the defects in vessel formation by the RBP-J deficient EPC. These data suggested that the RBP-J-mediated Notch signaling regulated EPC mobilization and function, at least partially through dynamic modulation of CXCR4 expression. Our findings not only provide new insights into the regulation of EPC, but also have implications for clinical therapies using EPC in diseases.


Assuntos
Células Endoteliais/citologia , Regulação da Expressão Gênica , Proteína de Ligação a Sequências Sinal de Recombinação J de Imunoglobina/genética , Receptores CXCR4/biossíntese , Receptores Notch/metabolismo , Transdução de Sinais , Células-Tronco/citologia , Animais , Células da Medula Óssea/citologia , Transplante de Células , Hepatócitos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Receptores CXCR4/química , Regeneração
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