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Xiaohui Wang Zhuyao Wang Yuzhen YaoJingjin Li Xiaojin ZhangChuanfu Li Yunlin ChengGuoxian Ding Li Liu Zhengnian Ding 《Biochimica et Biophysica Acta (BBA)/Molecular Cell Research》2011,1813(5):827-838
Background
Neurite outgrowth is an important aspect of neuronal plasticity and regeneration after neuronal injury. Alpha-lipoic acid (LA) has been used as a therapeutic approach for a variety of neural disorders. We recently reported that LA prevents local anesthetics-induced neurite loss. In this study, we hypothesized that LA administration promotes neurite outgrowth.Methods
To test our hypothesis, we treated mouse neuroblastoma N2a cells and primary neurons with LA. Neurite outgrowth was evaluated by examination of morphological changes and by immunocytochemistry for β-tubulin-3. ROS production was examined, as were the phosphorylation levels of ERK and Akt. In separate experiments, we determined the effects of the inhibition of ERK or PI3K/Akt as well as ROS production on LA-induced neurite outgrowth.Results
LA promoted significantly neurite outgrowth in a time- and concentration-dependent manner. LA stimulation significantly increased the phosphorylation levels of both Akt and ERK and transiently induced ROS production. PI3K/Akt inhibition did not affect LA-induced neurite outgrowth. However, the inhibition of ERK activation completely abolished LA-induced neurite outgrowth. Importantly, the prevention of ROS production by antioxidants attenuated LA-stimulated ERK activation and completely abolished LA-promoted neurite outgrowth.Conclusion
Our data suggest that LA stimulates neurite outgrowth through the activation of ERK signaling, an effect mediated through a ROS-dependent mechanism. 相似文献103.
在生理状态下,细胞通过自噬清除衰老细胞器和异常长寿蛋白质,维持自身结构和功能的衡定,参与胚胎发育、免疫调节和延长寿命。病理状态下细胞自噬水平显著升高,以耐受饥饿、缺血和凋亡。自噬功能障碍与某些慢性感染疾病、神经变性疾病、溶酶体贮积症和肿瘤等密切相关。掌握和合理应用自噬研究技术对于提高细胞自噬研究水平有着重要意义。该文对哺乳类细胞自噬研究技术进展及其应用作了概述。 相似文献
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茶树(Camellia sinensis L.)种植是亚热带丘陵山区主要的土地利用类型,茶园种植模式是影响土壤细菌群落结构的主要人为因素。为揭示种植模式和坡位对土壤细菌群落结构和功能的影响,选取两种不同种植模式(常规和有机种植模式)和3个坡位(上、中、下坡位)表层土壤(0-20cm)为对象,采用野外调查、Illumina Miseq高通量测序和PICRUSt2功能预测相结合的研究方法,研究不同种植模式和坡位下土壤细菌群落结构和功能特征,阐明土壤理化性质对土壤细菌群落结构的影响,预测土壤细菌功能特征。研究结果表明:(1)与常规种植模式相比,有机种植模式茶园土壤细菌Alpha多样性有所降低,其中中坡位常规茶园土壤细菌Sobs和Simpson指数显著高于有机茶园(P<0.05);从坡面尺度看,两种种植模式下土壤细菌Alpha多样性指标均以中坡位最高,其中常规茶园中坡位土壤细菌Ace和Simpson指数均显著高于下坡位(P<0.05)。(2)各样地茶园土壤细菌共获得29个门82个纲190个目316个科517个属929个种,主要细菌优势门为绿弯菌门(Chloroflexi)、放线菌门(Actinobacterita)、变形菌门(Proteobacteria)、酸杆菌门(Acidobacteria)。土壤细菌群落优势属以AD3、热酸菌属(Acidothermus)、norank_f__norank_o__Elsterales和norank_f__Xanthobacteraceae为主。(3)主坐标分析(PCoA)显示,不同种植模式的茶园土壤细菌群落结构存在明显差异,常规种植模式下不同坡位之间的土壤细菌群落结构有显著差异(P<0.05),有机种植下不同坡位之间的土壤细菌群落结构无显著差异。置换多元方差分析(PERMANOVA)结果表明不同种植模式的土壤细菌群落结构差异显著(P<0.05),而不同坡位土壤细菌群落结构无显著差异(P>0.05),说明种植模式对茶园土壤细菌群落结构的影响更大。组间群落差异分析(LEfSe)表明,57个差异物种对种植模式非常敏感,不同种植模式富集了不同的细菌类群。(4) PICRUSt2功能预测共获得6个一级功能层和46个二级功能层,表现出功能上的丰富性,土壤细菌群落在代谢、遗传信息处理和环境信息方面功能活跃。有机种植模式提高了土壤细菌碳水化合物代谢、氨基酸代谢、膜运输、信号转导、脂质代谢及外源生物降解与代谢功能。(5)相关分析和冗余分析结果表明,土壤碱解氮、速效磷、全磷、全钾和pH是影响土壤细菌群落丰度和多样性的主要影响因子。总体而言,有机种植模式改变了茶园土壤细菌群落结构和代谢功能,增加土壤有益细菌的数量,有利于保持茶园土壤可持续的生态环境。 相似文献
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Cervical cancer is a cancer arising from the cervix, and it is the fourth most common cause of death in women. Overexpression of fibronectin 1 (FN1) was observed in many tumors and associated with the survival and metastasis of cancer cells. However, the mechanism by which FN1 promotes cervical cancer cell viability, migration, adhesion, and invasion, and inhibits cell apoptosis through focal adhesion kinase (FAK) signaling pathway remains to be investigated. Our results demonstrated that FN1 was upregulated in patients with cervical cancer and higher FN1 expression correlated with a poor prognosis for patients with cervical cancer. FN1 knockdown by small interfering RNA (siRNA) inhibited SiHa cell viability, migration, invasion, and adhesion, and promoted cell apoptosis. FN1 overexpression in CaSki cell promoted cell viability, migration, invasion, and adhesion, and inhibited cell apoptosis. Further, phosphorylation of FAK, a main downstream signaling molecule of FN1, and the protein expression of Bcl-2/Bax, matrix metalloproteinase 2 (MMP-2), matrix metalloproteinase 9 (MMP-9), and N-cadherin was upregulated in CaSki cells with FN1 overexpression, but caspase-3 protein expression was downregulated. The FAK phosphorylation inhibitor PF573228 inhibited FN1 overexpression-induced expression of those proteins in CaSki cells with FN1 overexpression. In vivo experiment demonstrated that FN1 knockdown significantly inhibited FN1 expression, phosphorylation of FAK, and tumor growth in xenograft from the nude mice. These results suggest that FN1 regulates the viability, apoptosis, migration, invasion, and adhesion of cervical cancer cells through the FAK signaling pathway and is a potential therapeutic target in the treatment of cervical cancer. 相似文献
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Oral squamous cell carcinoma (OSCC) is a common human malignancy with high incidence rate and poor prognosis. Although the polycomb group protein enhancer of zeste homolog 2 (EZH2) plays a crucial role in cell proliferation and differentiation during the occurrence and development progress of several kinds of malignant tumors, the impact of EZH2 on the development and progression of OSCC is unclear. In this study, we demonstrate that EZH2 is overexpressed in OSCC cells and clinical tissue. With in vitro RNAi analysis, we generated stable EZH2 knocking down cell lines from two OSCC cell lines, with two sh-RNAs targeting to EZH2, respectively. We found that knocking down of EZH2 could decrease the proliferation ability and induce apoptosis of OSCC cells. Moreover, we demonstrated that of EZH2 inhibition decreased the migration and metastasis of OSCC cells. In conclusion, the results of the current study demonstrated an association between EZH2 expression and OSCC cell development. We recommend that EZH2 acts as an oncogene and plays an important role in OSCC carcinogenesis. 相似文献