线粒体与细胞凋亡

通过近几年对细胞凋亡的研究 ,人们发现线粒体在凋亡后期仍能保持完好的功能结构 ,其在凋亡中的作用日益受到关注。1　凋亡相关基因在细胞内的定位B细胞淋巴瘤 /白血病基因 - 2 (Bcl- 2 )及其家族是调节细胞程序性死亡的主要原因 ,要探明其对凋亡的调节机制需要完善的膜定位。过去有报道认为 Bcl- 2定位于线粒体内膜 ,现通过共焦显微镜、免疫电镜及化学分离法进行了大量的研究 ,发现 Bcl- 2定位于核膜的细胞胞浆面、线粒体外膜及内质网。Bcl- 2家族中的另外一些基因如 Bcl- X1 及 Bcl- Xs,有人认为其定位于线粒体 ,并另有人认为是在线粒…     

NGF与细胞凋亡

神经长生因子是一种影响神经细胞发育、存活的多能神经营养因子，其中枢和周围效应与神经细胞凋亡密切相关。本文对NGF与神经系统发育、神经损伤及疾病过程中所发生的细胞凋亡的关系以及NGF的抗凋亡作用等方面的研究状况进行了综述。     

重型肝炎与细胞凋亡

细胞凋亡(Apoptosis)由英国学者Kerr于1972年首先提出，用以描述在形态学上有别于细胞坏死的一种细胞死亡方式，其本质是基因调控的程序性细胞死亡过程．又称细胞程序性死亡。凋亡是个主动、耗能的基因DNA断化而最终导致细胞死亡的过程．其作为一种生理现象在胚胎发育、免疫与造血系统成熟、维持正常组织和器官细胞数的恒定生长平衡等方面均发挥重要作用，但细胞凋亡异常，也参与多种疾病发生。     

活性氧、线粒体与细胞凋亡

近年来，在生命科学研究领域一种新兴学科正方兴未艾，愈来愈受到医学家、生物学家、免疫学家及其相关学科研究者的瞩目，即细胞凋亡（apoptosis）亦称程序性细胞死亡（programmed ecll death，PCD）的研究。凋亡过程的紊乱与许多疾病直接或间接相关，如肿瘤、自身免疫性疾病、地方病等。细胞凋亡不仅是一种特殊的细胞死亡方式，同时也具有重要的生物学意义和复杂的分子生物学机制。许多因素参与细胞凋亡过程的调节，本文就活性氧（reactive oxygen species，ROS）线粒体与细胞凋亡的关系作一概述。     

线粒体与细胞凋亡的研究进展

线粒体在细胞凋亡和肿瘤的发生及耐药中有重要作用,线粒体信号转导通路在细胞能量代谢、细胞凋亡启动中的特殊地位,及线粒体DNA(mtDNA)突变与肿瘤耐药的密切关系,使探讨线粒体与肿瘤细胞凋亡的相关性研究具有重要的理论和临床意义。     

细胞凋亡在肾脏疾病中的研究进展

细胞凋亡（apoptosis）又称程序化细胞死亡（programmed cell death，PCD），是多细胞有机体为调控机体发育、维护内环境稳定，由基因控制的细胞主动死亡过程。细胞内外的凋亡诱导因素通过多种信号转导机制来调控细胞凋亡过程，其中Fas／FasL信号系统是重要的凋亡信号转导系统之一，Fas是细胞表面Ⅰ型跨膜蛋白，Fas配体（Fas ligand，FasL）为Ⅱ型跨膜蛋白，FasL或特异性Fas抗体与Fas相互作用可导致细胞凋亡。大量事实表明，细胞凋亡参与了肾脏正常发育及肾疾病发生等多个过程，在肾脏疾病的发生发展过程中发挥着有益或有害的作用。     

缺血性脑损伤与神经细胞凋亡

一、神经细胞凋亡 细胞凋亡在神经系统的发育中起着重要的作用．外周和中枢神经系统发育过程中约有15％-85％的细胞死亡。这种死亡是细胞的凋亡而非细胞的坏死,其目的在于建立某种早期模式和清除某种细胞系,从而为形成更加复杂的神经网络而奠定基础。细胞凋亡有两方面的作用：一方面维持正常细胞的代谢,另一方面却破坏了人体的正常生理功能,如正常的组织细胞的发育或肿瘤的形成。     

线粒体DNA与细胞凋亡相关性研究进展

细胞凋亡亦称程序性细胞死亡是一种重要的生命现象,不仅出现在生理情况下,更与肿瘤、自身免疫性疾病及退行性神经病变等多种疾病密切相关。细胞凋亡过程中许多重要事件与线粒体有关,例如半胱氨酸蛋白酶家族激活剂的释放(如细胞色素C)、电子传递链的变化、线粒体跨膜电位的消失、异常的细胞氧化-还原反应及促进凋亡或抑制凋亡的bcl- 2家族的参与等。而线粒体又受核DNA( n DNA)和线粒体DNA( mt DNA)的双重控制,其中mt DNA控制线粒体的呼吸作用等基本特征。因此,近年来mt DNA与细胞凋亡之间的相关性研究日益受到重视,现将其研究进展综…     

线粒体与心肌细胞凋亡的研究进展

心肌细胞凋亡 (ａｐｏｐｔｏｓｉｓ)是心肌细胞的一种程序性死亡 ,它在心脏的发育及心力衰竭、原发性高血压、心律失常等许多心脏疾病的病理生理中起着重要作用。线粒体是细胞产生能量的细胞器 ,维持机体生命活动所需的能量 ,90 %以上都是由它以三磷酸腺苷 (ＡＴＰ)形式产生。现在的研究证实 ,线粒体在介导细胞凋亡中起着重要作用。在心肌细胞中 ,线粒体约占心肌细胞总体积的 4 5 %。研究发现 ,在心肌细胞凋亡时 ,线粒体结构与功能发生明显改变 ,且与心肌细胞凋亡显著相关[1 3] 。本文主要综述线粒体在心肌细胞凋亡中的作用及其意义。一、…     

羟基喜树碱诱导SMMC-7721细胞凋亡时线粒体凋亡诱导因子的转位研究

目的研究羟基喜树碱诱导肝癌细胞株SMMC-7721凋亡时线粒体凋亡相关蛋白凋亡诱导因子表达及从线粒体发生核转位的变化.方法用80 μg/ml羟基喜树碱作用于肝癌细胞株SMMC-7721后,用吖啶橙/溴化乙啶染色法观察细胞凋亡现象;用电子显微镜观察线粒体超微结构;分别用逆转录聚合酶链反应、Western blot检测凋亡诱导因子在mRNA与蛋白质水平表达的变化;用激光共聚焦显微镜观察凋亡诱导因子在细胞凋亡时从线粒体到核的迁移变化.结果 80μg/ml羟基喜树碱作用SMMC-7721细胞后,吖啶橙/溴化乙啶荧光双重染色可见细胞体积缩小、细胞皱缩、核碎裂等典型细胞凋亡形态学改变;超微结构观察发现线粒体肿胀;细胞凋亡时凋亡诱导因子在mRNA与蛋白质水平上的表达与对照组细胞相比没有明显变化,但凋亡诱导因子发生了从线粒体到核的迁移. 结论羟基喜树碱可以通过线粒体途径诱导人肝癌细胞发生凋亡;在线粒体凋亡途径中,线粒体凋亡相关蛋白凋亡诱导因子从线粒体释放并发生核转位可能与羟基喜树碱诱导细胞凋亡密切相关.     

Thymocyte apoptosis a model of programmed cell death.

Recently there has been widespread appreciation for the role of apoptosis, or programmed cell death, in the maintenance of tissue structure and function. Studies in several model systems have revealed that apoptosis is profoundly regulated by a number of diverse hormones, including steroids. The killing of immature thymic lymphocytes by glucocorticoids has emerged as an important model to define the biochemical mechanisms that mediate the programmed cell death process. Using this model, we, and others, have shown that lymphocytes degrade their DNA in response to glucocorticoids. The onset of DNA degradation precedes cell death and is the probable cause of apoptosis. This unique response to endocrine signal transduction will undoubtedly promise new insights into the mechanism of hormone action.     

程序性细胞死亡因子4过表达对胃癌细胞BGC823凋亡及凋亡调控蛋白的影响

目的通过稳定转染程序性细胞死亡因子4（programmed cell death4,PDCIM）基因至胃癌细胞BGC823中,观察过表达PDCD4对BGC823凋亡的作用及对凋亡相关调控蛋白Akt／p-Akt、FLIP、caspase-8及cleaved-caspase-8的影响。方法构建针对人PDCD4的真核表达载体并转染至BGC823细胞,Annexin V—FITC／PI联合流式细胞仪检测细胞凋亡,Western Blot检测蛋白的表达。结果成功构建PDCD4真核表达载体并转染至BGC823中,获得稳定过表达PDCD4的细胞模型,过表达PDCD4的BGC823细胞凋亡率（10．82％±1．29％）较未转染组（5．06％±0．83％）明显升高（P〈0．05）。转染PDCD4后,Akt／p-Akt表达（0．25±0．04／0．06±0．01）较未转染组（0．65±0．09／0．18±0．02）明显降低（P〈0．01）,FLIP蛋白在转染组中的表达（0．12±0．01）较未转染组中的表达（0．48±0．06）明显降低（P〈0．01）,而转染组caspase-8（0．36±0．07）及cleaved—caspasc-8（0．24±0．05）较未转染组caspase-8（0．18±0．04）及cleaved-caspase-8（0．11±0．02）明显升高（P〈0．05）。结论PDCD4过表达可促进胃癌细胞BGC823的凋亡,并且抑制Akt和FLIP的表达,从而促进caspase-8的活性。     

High-dose mitoxantrone induces programmed cell death or apoptosis in human myeloid leukemia cells

Mitoxantrone has been shown in vitro to exhibit a steep dose-response relationship with respect to the clonogenic survival of acute myeloid leukemia cells. In this report, we show that 1-hour exposure of human myeloid leukemia HL-60 and KG-1 cells to mitoxantrone concentrations ranging between 0.1 and 10.0 mumol/L induced internucleosomal DNA fragmentation of approximately 200-bp integer multiples, characteristic of cells undergoing programmed cell death (PCD) or apoptosis. Mitoxantrone-mediated PCD was associated with a steep inhibition of the clonogenic survival of the leukemic cells. In addition, intracellularly, mitoxantrone-induced PCD was associated with a marked induction of c-jun and significant repression of c-myc and BCL-2 oncogenes. Pretreatment with the protein kinase C stimulator phorbol myristate acetate enhanced mitoxantrone-induced internucleosomal DNA fragmentation, whereas protein kinase C inhibitors staurosporine and H7 had no effect. These findings suggest that PCD is a potential mechanism underlying the steep dose-response relationship of mitoxantrone to the inhibition of clonogenic survival of acute myeloid leukemia cells.     

NF-κB与细胞凋亡

NF-kB家族及其介导的细胞信号转导通路在细胞凋亡中的作用是国内外研究的热点.研究发现,NF-kB信号转导途径可以通过多种途径抑制细胞凋亡,与IAPs家族、Bcl-2家族、TRAF家族、JNK、FLIP、A20、Gadd45β、MnSOD等有很大关系,但其具体机制尚未完全清楚.通过抑制NF-kB信号转导途径的激活,促进细胞凋亡,可能成为治疗免疫、炎症、肿瘤等疾病的新途径.此外,近年的研究证明NF-kB尚具有促细胞凋亡的作用,并发现NF-kB亚单位的种类及数量在细胞凋亡中起着决定性的作用,为疾病的治疗提供了新的策略.本文就NF-kB与细胞凋亡关系的研究进展作一综述.     

Expression of a specific marker of avian programmed cell death in both apoptosis and necrosis.

Apoptosis and necrosis are two types of cell death with different morphologic features. We report here the isolation of a monoclonal antibody, BV2, that specifically recognizes cells undergoing developmental programmed cell death in different tissues of the chicken and zebra-finch embryos. The antigen recognized by BV2 monoclonal antibody is detected in vitro in primary chicken embryonic fibroblasts induced to die by actinomycin D, as well as fibroblasts induced to die by chemical anoxia. The expression of this specific antigen during necrosis appears to require active protein synthesis. These findings provide evidence that cells from different embryonic tissues undergoing programmed cell death during vertebrate development express similar antigens and indicate that apoptosis and necrosis may share similar biochemical features.     

Association between programmed cell death ligand 1 expression and thyroid cancer: A meta-analysis

Background:Programmed cell death ligand 1 (PD-L1), which is highly expressed in a variety of malignant tumors, is closely related to clinicopathological features and prognosis. However, there are few studies on the potential effects of PD-L1 on thyroid carcinoma, the incidence of which has shown an upward trend worldwide. This study aimed to explore the association between PD-L1 expression and clinicopathological features and prognosis of thyroid cancer.Methods:An elaborate retrieval was performed using Medline, PubMed, Cochrane Library, EMBASE, Web of Science, WanFang databases, and China National Knowledge Infrastructure to determine the association between PD-L1 expression and disease-free survival (DFS), overall survival (OS), and clinicopathological features in patients with thyroid cancer. Study selection, data extraction, risk assessment, and data synthesis were performed independently by 2 reviewers. In this meta-analysis, RevMan 5.3 and Stata 15.1 were used for bias risk assessment and data synthesis.Results:After a detailed search, 2546 cases reported in 13 articles were included in this meta-analysis. The outcomes revealed that high expression of PD-L1 in patients with thyroid cancer was associated with poor DFS (hazard ratio [HR] = 3.37, 95% confidence interval [CI] 2.54–4.48, P < .00001) and OS (HR = 2.52, 95% CI: 1.20–5.32, P = .01). High PD-L1 expression was associated with tumor size ≥2 cm, tumor recurrence, extrathyroidal extension, concurrent thyroiditis, unifocal tumor, and absence of psammoma body (P < .05). Subgroup analysis showed that positive expression of PD-L1 was related to poor prognosis for DFS of non-medullary thyroid carcinoma, and the overexpression of PD-L1 in differentiated thyroid carcinoma (DTC) was related to tumor recurrence, concurrent thyroiditis, extrathyroidal extension, unifocal DTC, late stage DTC, and BRAF^V600E mutation in DTC.Conclusion:PD-L1 is a significant predictor of prognosis and malignancy of thyroid cancer (especially DTC), and PD-L1 inhibitors may be a promising therapeutic option for refractory thyroid cancer in the future.     

Expression of programmed cell death 1 and programmed cell death ligand 1 in extranodal NK/T-cell lymphoma,nasal type

Programmed cell death-1 (PD-1) and programmed cell death-ligand 1 (PD-L1) are new therapeutic targets in cancer immunotherapy. The aim of this study was to investigate the clinicopathological characteristics of PD-1 and PD-L1 expression in extranodal natural killer/T?cell lymphoma, nasal type (ENKTL). We performed PD-1 and PD-L1 immunostaining in 79 ENKTL biopsy samples and retrospectively analyzed medical records of all 79 patients from four tertiary referral hospitals. The expression of PD-1 and PD-L1 by tumor cells and/or infiltrating immune cells was evaluated. The expression rates of PD-L1 in tumor cells and infiltrating immune cells were 79.7 and 78.5 %, respectively, whereas PD-1 in tumor cells and infiltrating immune cells were 1.3 and 11.4 %. The PD-L1 positivity in tumor cells and infiltrating immune cells was significantly associated with low international prognostic index (IPI) (P?=?0.044 and 0.037, respectively). Patients with normal range of serum lactate dehydrogenase demonstrated a significantly higher PD-L1 positivity in tumor cells (P?=?0.020). PD-L1-positive patients had a trend toward better overall survival compared with that in patients with PD-L1-negative in tumor cells and infiltrating immune cells (P?=?0.498 and 0.435, respectively). The expression rate of PD-L1 was up to 79.7 % in ENKTL, while PD-1 expression rate was very low. This is the first report describing the clinicopathological features and survival outcome according to expression of PD-1 and PD-L1 in ENKTL.     

程序性细胞死亡蛋白1/程序性细胞死亡配体信号通路在结核病免疫调控中的研究进展

程序性细胞死亡蛋白1与程序性细胞死亡配体(包括程序性细胞死亡配体1和程序性细胞死亡配体2)属于抑制性共刺激分子,在结核病的免疫应答中发挥着重要作用。本文就其通路的结构和功能及其在结核病肺泡巨噬细胞和T细胞亚群、不同结核病分类和结核病不同治疗阶段的免疫调控作用进行综述,以期能为开辟结核病诊断和治疗新方法提供新思路。