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991.
线粒体是细胞新陈代谢和生长发育过程中重要的细胞器,能够为细胞的生命活动提供能量和底物.当细胞处于恶劣环境时,线粒体通过自噬清除不需要或损伤的线粒体来减轻负荷,补充营养物质,适应恶劣的环境.线粒体自噬对维持细胞生存,抵御环境压力,衰老和凋亡过程起着重要作用.线粒体自噬的异常将导致多种疾病,如:神经退行性变、心脏病、糖尿病以及肿瘤等.随着人们生活习惯的改变,结直肠癌的发病率和死亡率逐年增加,成为中国最常见的恶性肿瘤之一,结直肠癌与线粒体自噬的研究也成为该领域的研究热点.明确线粒体自噬对结直肠癌的作用,有助于进一步了解结直肠癌的发病机制,并为结直肠癌的诊断和治疗提供新的方向和思路.因此,本文将着重阐述线粒体自噬的发生机制及其与结直肠癌的关系.  相似文献   
992.
Purpose: Excess reactive oxygen species are detrimental to wound repair. Remifentanil decreases reactive oxygen species generation and inflammatory response; however, its effects on oxidative cell injury are not completely understood. Therefore, we investigated the effects of remifentanil on human keratinocytes under hydrogen peroxide-induced oxidative stress and the correlation of these effects with autophagy. Materials and Methods: Human keratinocytes (HaCaT cell line) were randomly assigned to four groups: control, hydrogen peroxide, remifentanil pretreatment + hydrogen peroxide, and 3-methyladenine + remifentanil pretreatment + hydrogen peroxide. The MTT assay was performed to analyze cell viability. Apoptotic cell death was measured by Hoechst staining. A scratch assay was used to measure cell migration. The role of autophagy was ascertained by autophagosome staining and western blot analysis of autophagy-related proteins. Results: Compared with the control group, the hydrogen peroxide group showed decreased cell viability, which was improved by remifentanil pretreatment. Hydrogen peroxide-induced apoptotic cell death and delayed cell migration were also improved by remifentanil pretreatment. Western blot analysis showed that the expression of autophagy-related proteins significantly increased in the remifentanil pretreatment + hydrogen peroxide group compared with that in the hydrogen peroxide group. Conclusions: This study demonstrated that remifentanil pretreatment ameliorates hydrogen peroxide-induced oxidative injury in human keratinocytes. In addition, our results show that the antioxidative effect of remifentanil against hydrogen peroxide-induced oxidative injury was mediated by autophagy.  相似文献   
993.
目的:探讨塞来昔布对急性髓细胞白血病(AML)HL-60细胞和HL-60A细胞的活力、凋亡及自噬的影响。方法:用不同浓度的(0、20、40、60、80和100μmol/L)塞来昔布作用于HL-60细胞和HL-60A细胞,24h、48h和72h后用MTT法检测细胞活力。用流式细胞术检测塞来昔布作用HL-60细胞和HL-60A细胞24 h后的凋亡率。用Western blot法检测凋亡相关蛋白cleaved caspase-3、cleaved PARP,自噬相关蛋白LC3、P62,以及mTOR信号途径相关蛋白。结果:塞来昔布作用于HL-60细胞24h、48h和72h的IC_(50)分别为49.4μmol/L、32.0μmol/L和25.1μmol/L,对于HL-60A细胞,相应的IC_(50)分别是69.1μmol/L、42.5μmol/L和29.6μmol/L。塞来昔布作用24h后,流式细胞术检测显示HL-60细胞中Annexin-V~+PI~-、Annexin-V~+PI~+及Annexin-V~-PI~+细胞的比例增多;HL-60A细胞中Annexin-V~+PI~-及Annexin-V~+PI~+细胞的比例增多。Western blot实验结果显示塞来昔布作用后,cleaved caspase-3和cleaved PARP的蛋白水平增高,提示该凋亡作用是通过caspase途径的。自噬相关蛋白LC3Ⅱ及P62的表达均增加,mTOR、p-mTOR以及下游的4-EBP、p-4-EBP的蛋白水平没有变化,说明塞来昔布能够抑制AML细胞自噬,该作用与mTOR途径无关。结论:塞来昔布对HL-60细胞和HL-60A细胞活力的抑制作用呈浓度以及时间依赖性,该作用与塞来昔布诱导细胞凋亡及坏死有关。塞来昔布能够通过非mTOR依赖途径抑制AML细胞自噬,有望联合应用于AML的治疗,有助于增强某些引起保护性自噬的化疗药物的细胞毒作用。  相似文献   
994.
目的:研究不同浓度的自噬抑制剂氯喹(CQ)对活化的大鼠肝星状细胞系HSC-T6中Ⅰ、Ⅲ型胶原表达的影响及可能机制。方法:应用转化生长因子β1(TGF-β1)活化HSC-T6细胞,给予CQ干预24 h。实验分组为:control组、TGF-β1组、TGF-β1+CQ(15μmol/L)组、TGF-β1+CQ(30μmol/L)组和TGF-β1+CQ(60μmol/L)组。采用Western blot技术检测微管相关蛋白轻链3(LC3)比值LC3-Ⅱ/LC3-Ⅰ、自噬靶蛋白P62、α-平滑肌肌动蛋白(α-SMA)、Ⅰ型胶原、Ⅲ型胶原、基质金属蛋白酶13(MMP-13)、金属蛋白酶组织抑制物1(TIMP-1)和TIMP-2的表达情况;免疫细胞化学检测Ⅰ、Ⅲ型胶原的表达;RT-q PCR检测Ⅰ型胶原、Ⅲ型胶原、MMP-13、TIMP-1和TIMP-2mRNA的表达变化。结果:CQ干预后LC3-Ⅱ/LC3-Ⅰ比值明显升高且呈剂量依赖性;P62蛋白表达TGF-β1+CQ组均显著高于TGF-β1组(P0.01)。TGF-β1组的Ⅰ、Ⅲ型胶原表达量较control组显著增加,TGF-β1+CQ组较TGF-β1组也有明显增加。α-SMA的表达在TGF-β1组和TGF-β1+CQ组均显著高于control组(P0.05),而TGF-β1组和TGF-β1+CQ各组之间无显著差异。MMP-13表达在TGF-β1+CQ组较TGF-β1组显著下降(P0.05);TIMP-1和TIMP-2在TGF-β1+CQ组较TGF-β1组显著升高(P0.05),且呈剂量依赖性。结论:自噬抑制剂CQ能显著增加HSC-T6细胞中Ⅰ、Ⅲ型胶原的表达并呈剂量依赖性,这可能与其上调TIMP-1及TIMP-2的表达并抑制MMP-13表达有关。  相似文献   
995.
Autophagy is an intracellular “self-eating” process that is closely related to inflammation and cellular immunity. New studies indicate that autophagy is also involved in tumor suppression. The anti-inflammatory cytokine interleukin-37 (IL-37) has been shown to have tumor-suppressive abilities in hepatocellular carcinoma (HCC). Notably, autophagy appears to play a dual role in the development of HCC and may be involved in both tumorigenesis and tumor suppression. However, the potential role of IL-37 in autophagy is currently unknown. In this study, we investigated the effect of IL-37 on autophagy in multiple HCC cell lines. In doing so, we found that IL-37 inhibits proliferation in HCC cells and also induces autophagy and apoptosis in the SMMC-7721 and Huh-7 cell lines. Further experiments revealed that IL-37 treatment reduced the levels of phosphorylated protein kinase B (p-AKT), phosphorylated mammalian target of rapamycin (p-mTOR), phosphorylated p70 ribosomal protein s6 kinase (p-p70S6K) and phosphorylated 4E-binding protein 1 (4E-BP1). Moreover, treatment with an AKT agonist, insulin-like growth factor 1 (IGF-1), reversed these IL-37-mediated effects on autophagy, and treatment with an phosphoinositide-3-kinase (PI3K)/AKT inhibitor, LY294002, mimicked the effects of IL-37. Taken together, these results indicate that IL-37 regulates autophagy in SMMC-7721 and Huh-7 cells via inhibition of the PI3K/AKT/mTOR signaling pathway.  相似文献   
996.
Alzheimer’s disease (AD) is a common form of dementia in aged people, which is defined by two pathological characteristics: β-amyloid protein (Aβ) deposition and tau hyperphosphorylation. Although the mechanisms of AD development are still being debated, a series of evidence supports the idea that metals, such as copper, iron, zinc, magnesium and aluminium, are involved in the pathogenesis of the disease. In particular, the processes of Aβ deposition in senile plaques (SP) and the inclusion of phosphorylated tau in neurofibrillary tangles (NFTs) are markedly influenced by alterations in the homeostasis of the aforementioned metal ions. Moreover, the mechanisms of oxidative stress, synaptic plasticity, neurotoxicity, autophagy and apoptosis mediate the effects of metal ions-induced the aggregation state of Aβ and phosphorylated tau on AD development. More importantly, imbalance of these mechanisms finally caused cognitive decline in different experiment models. Collectively, reconstructing the signaling network that regulates AD progression by metal ions may provide novel insights for developing chelators specific for metal ions to combat AD.  相似文献   
997.
The role of autophagy in retinal ganglion cell (RGC) death is still controversial. Several studies focused on RGC body death, although the axonal degeneration pathway in the optic nerve has not been well documented in spite of evidence that the mechanisms of degeneration of neuronal cell bodies and their axons differ. Axonal degeneration of RGCs is a hallmark of glaucoma, and a pattern of localized retinal nerve fiber layer defects in glaucoma patients indicates that axonal degeneration may precede RGC body death in this condition. As models of preceding axonal degeneration, both the tumor necrosis factor (TNF) injection model and hypertensive glaucoma model may be useful in understanding the mechanism of axonal degeneration of RGCs, and the concept of axonal protection can be an attractive approach to the prevention of neurodegenerative optic nerve disease. Since mitochondria play crucial roles in glaucomatous optic neuropathy and can themselves serve as a part of the autophagosome, it seems that mitochondrial function may alter autophagy machinery. Like other neurodegenerative diseases, optic nerve degeneration may exhibit autophagic flux impairment resulting from elevated intraocular pressure, TNF, traumatic injury, ischemia, oxidative stress, and aging. As a model of aging, we used senescence-accelerated mice to provide new insights. In this review, we attempt to describe the relationship between autophagy and recently reported noteworthy factors including Nmnat, ROCK, and SIRT1 in the degeneration of RGCs and their axons and propose possible mechanisms of axonal protection via modulation of autophagy machinery.  相似文献   
998.
999.
Despite its dual role in determining cell fate in a wide array of solid cancer cell lines, autophagy has been robustly shown to suppress or kill acute myeloid leukemia cells via degradation of the oncogenic fusion protein that drives leukemogenesis. However, autophagy also induces the demise of acute leukemia cells that do not express the known fusion protein, though the molecular mechanism remains elusive. Nevertheless, since it can induce cooperation with apoptosis and differentiation in response to autophagic signals, autophagy can be manipulated for a better therapy on acute myeloid leukemia.  相似文献   
1000.
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