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1.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-878327

RESUMO

Objective@#The aim of this study was to explore the ototoxicity of toluene in the early development of zebrafish embryos/larvae.@*Methods@#Zebrafish were utilized to explore the ototoxicity of toluene. Locomotion analysis, immunofluorescence, and qPCR were used to understand the phenotypes and molecular mechanisms of toluene ototoxicity.@*Results@#The results demonstrated that at 2 mmol/L, toluene induced zebrafish larvae death at 120 hours post fertilization (hpf) at a rate of 25.79% and inhibited the rate of hatching at 72 hpf. Furthermore, toluene exposure inhibited the distance travelled and average swimming velocity of zebrafish larvae while increasing the frequency of movements. As shown by fluorescence staining of hair cells, toluene inhibited the formation of lateral line neuromasts and middle line 1 (Ml @*Conclusion@#This study indicated that toluene may affect the development of both the inner ear and lateral line systems in zebrafish, while the lateral line system may be more sensitive to toluene than the inner ear.


Assuntos
Animais , Orelha Interna/crescimento & desenvolvimento , Embrião não Mamífero/efeitos dos fármacos , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Células Ciliadas Auditivas/metabolismo , Sistema da Linha Lateral/crescimento & desenvolvimento , Locomoção/efeitos dos fármacos , Ototoxicidade/fisiopatologia , Tolueno/toxicidade , Peixe-Zebra
2.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-270615

RESUMO

<p><b>OBJECTIVE</b>To investigate the role of extracellular signal-regulated kinase (ERK) in apoptosis of human colon cancer (HCT116) cells.</p><p><b>METHODS</b>After the HCT116 cells were pretreated with specific ERK inhibitor (U0126) or specific siRNA and exposed to 10 mmol/L sodium butyrate (NaBT) for 24 h, their apoptosis was detected by flow cytometry, levels of SphK2 and ERK protein were measured by Western blot, and translocation of SphK2 was assayed by immunofluorescence microscopy.</p><p><b>RESULTS</b>The U0126 and siRNAs specific for SphK2 blocked the export of SphK2 from nuclei to cytoplasm and increased the apoptosis of HCT116 cells following NaBT exposure. Over-expression of PKD decreased NaBT-induced apoptosis of HCT116 cells, which was reversed by U0126. Furthermore, transfection of HCT116 cells with constitutively activated PKD plasmids recovered the U0126-blocked export of SphK2.</p><p><b>CONCLUSION</b>ERK regulates the export of SphK2 and apoptosis of HCT116 cells by modulating PKD. Modulation of these molecules may help increase the sensitivity of colon cancer cells to the physiologic anti-colon cancer agent, NaBT.</p>


Assuntos
Humanos , Apoptose , Fisiologia , Ácido Butírico , Farmacologia , MAP Quinases Reguladas por Sinal Extracelular , Metabolismo , Células HCT116 , Fosfotransferases (Aceptor do Grupo Álcool) , Genética , Metabolismo , Proteína Quinase C , Genética , Metabolismo , RNA Interferente Pequeno , Transdução de Sinais
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