RESUMO
Lidocaine, a typical local anesthetic, has been shown to directly induce neurotoxicity in clinical settings. Dexmedetomidine (DEX) is an alpha-2-adrenoreceptor agonist that has been used as anxiolytic, sedative, and analgesic agent which has recently found to protect against lidocaine-induced neurotoxicity. Nicotinamide adenine dinucleotide-dependent deacetylase sirtuin-1 (SIRT1)/forkhead box O3 (FOXO3a) signaling is critical for maintaining neuronal function and regulation of the apoptotic pathway. In the present study, we designed in vitro and in vivo models to investigate the potential effects of lidocaine and DEX on SIRT1 and FOXO3a and to verify whether SIRT1/FOXO3a-mediated regulation of apoptosis is involved in DEX-induced neuroprotective effects against lidocaine. We found that in both PC12 cells and brains of mice, lidocaine decreased SIRT1 level through promoting the degradation of SIRT1 protein. Lidocaine also increased FOXO3a protein level and increased the acetylation of SIRT1 through inhibiting SIRT1. Upregulation of SIRT1 or downregulation of FOXO3a significantly inhibited lidocaine-induced changes in both cell viability and apoptosis. DEX significantly inhibited the lidocaine-induced decrease of SIRT1 protein level and increase of FOXO3a protein level and acetylation of FOXO3a. Downregulation of SIRT1 or upregulation of FOXO3a suppressed DEX-induced neuroprotective effects against lidocaine. The data suggest that SIRT1/FOXO3a is a potential novel target for alleviating lidocaine-induced neurotoxicity and provide more theoretical support for the use of DEX as an effective adjunct to alleviate chronic neurotoxicity induced by lidocaine.
Assuntos
Anestésicos Locais/toxicidade , Dexmedetomidina/farmacologia , Proteína Forkhead Box O3/antagonistas & inibidores , Lidocaína/antagonistas & inibidores , Fármacos Neuroprotetores/farmacologia , Sirtuína 1/antagonistas & inibidores , Acetilação , Animais , Apoptose/efeitos dos fármacos , Sobrevivência Celular , Regulação para Baixo/genética , Proteína Forkhead Box O3/genética , Proteína Forkhead Box O3/metabolismo , Lidocaína/toxicidade , Camundongos , Camundongos Endogâmicos C57BL , Células PC12 , RNA Interferente Pequeno/genética , Ratos , Sirtuína 1/genética , Sirtuína 1/metabolismoRESUMO
The binding of rare earth elements (REEs) with water-soluble polysaccharides of nondeproteinization and deproteinization in the leaves of the fern Dicranopteris dichotoma was studied by molecular activation analysis (MAA). Two cold-water-soluble polysaccharides (extracted by 75% ethanol and 90% ethanol, respectively) and one hot-water-soluble polysaccharide (extracted by 90% ethanol) were separated using biochemical separation techniques. The eight rare earth elements (La, Ce, Nd, Sm, Eu, Tb, Yb, and Lu) in these polysaccharides were determined by instrumental neutron activation analysis. Our new results showed that the REEs were bound firmly with the water-soluble polysaccharides in the plant, regardless of whether nondeproteinization or deproteinization was used. The molecular-weight (MW) measurement demonstrated that REEs were mainly bound with low-MW (10,000-20,000) polysaccharides.
Assuntos
Metais Terras Raras/química , Plantas/química , Polissacarídeos/química , Cromatografia por Troca Iônica , Análise de Ativação de Nêutrons , Solubilidade , TemperaturaRESUMO
It has been shown that the radiation resistance of some cruciferous plants is related to some natural radiation protection substances in these plants. Sinapine, which has shown radiation protection effects on barley, wheat and mouse, is one of such substances distributed in cruciferous plants. In this paper, the radiation protection effects of sinapine on Drosophila melanogaster in a sex-linked recessive lethal (SLRL) test system were observed. The sinapine solution could be fed to the D. melanogaster (Oregon K). 40 Gy X-irradiation induced SLRL mutation rate of 8.96%. However, if 10 mg/ml sinapine which was found to have no physiological toxicity or harmful effects on its reproductive function, was fed before 40 Gy X-irradiation, the SLRL mutation rate could be reduced to 0.40%, which was within the range of spontaneous SLRL mutation rate of Oregon K Drosophila, i.e. 0-0.4%. The potential of the using of the very strong radiation protection effects of sinapine in anticarcinogenesis was also discussed.
Assuntos
Colina/análogos & derivados , Mutação/efeitos da radiação , Protetores contra Radiação/farmacologia , Animais , Colina/farmacologia , Drosophila melanogaster/genética , Feminino , Ligação Genética , Masculino , Testes de Mutagenicidade , Mutação/efeitos dos fármacosRESUMO
The AtNRT1.1 (CHL1) transporter provides a primary mechanism for nitrate uptake in Arabidopsis and is expected to localize to the epidermis and cortex of the mature root, where the bulk of nitrate uptake occurs. Using fusions to GFP/GUS marker genes, we found CHL1 expression concentrated in the tips of primary and lateral roots, with very low signals in the epidermis and cortex. A time-course study showed that CHL1 is activated in the primary root tip early in seedling development and at the earliest stages of lateral root formation. Strong CHL1 expression also was found in shoots, concentrated in young leaves and developing flower buds but not in the shoot meristem. These expression patterns were confirmed by immunolocalization and led us to examine CHL1 function specifically in the growth of developing organs. chl1 mutants showed a reduction in the growth of nascent roots, stems, leaves, and flower buds. The growth of nascent primary roots was inhibited in the mutants even in the absence of added nitrate, whereas elongation of lateral root primordia was inhibited specifically at low nitrate and acidic pH. Interestingly, chl1 mutants also displayed a late-flowering phenotype. These results indicate that CHL1 is activated and functions in the growth of nascent organs in both shoots and roots during vegetative and reproductive growth.