死亡受体及线粒体途径与激活诱导T细胞凋亡

免疫系统形成了一系列确保激活的淋巴细胞能被有效清除的分子及信号途径，称之为激活诱导的细胞死亡。激活诱导的细胞死亡主要负责调节免疫细胞稳态及清除自身反应性淋巴细胞。死亡受体途径及线粒体死亡途径分别是细胞凋亡的外在途径和内在途径也参与了激活诱导的T细胞凋亡，本文就外周成熟T细胞凋亡相关的死亡受体途径，线粒体死亡途径及其相关调控机制研究进展作一综述。     

线粒体、内质网与细胞凋亡

细胞凋亡是近年来研究的热点,对其发生机制的研究对于肿瘤等多种疾病的治疗和免疫调节都具有重要价值。线粒体与内质网是细胞凋亡信号传导途径中起重要作用的细胞器。本文综述了凋亡过程中有关线粒体及内质网途径信号传导、调控机制的研究进展。     

死亡受体及线粒体途径与激活诱导T细胞凋亡

免疫系统形成了一系列确保激活的淋巴细胞能被有效清除的分子及信号途径 ,称之为激活诱导的细胞死亡。激活诱导的细胞死亡主要负责调节免疫细胞稳态及清除自身反应性淋巴细胞。死亡受体途径及线粒体死亡途径分别是细胞凋亡的外在途径和内在途径 ,也参与了激活诱导的T细胞凋亡 ,本文就外周成熟T细胞凋亡相关的死亡受体途径、线粒体死亡途径及其相关调控机制研究进展作一综述。     

009 死亡受体及线粒体途径与激活诱导T细胞凋亡

免疫系统形成了一系列确保激活的淋巴细胞能被有效清除的分子及信号途径,称之为激活诱导的细胞死亡.激活诱导的细胞死亡主要负责调节免疫细胞稳态及清除自身反应性淋巴细胞.死亡受体途径及线粒体死亡途径分别是细胞凋亡的外在途径和内在途径,也参与了激活诱导的T细胞凋亡,本文就外周成熟T细胞凋亡相关的死亡受体途径、线粒体死亡途径及其相关调控机制研究进展作一综述.     

肝脏中死亡受体的生物学和病理生物学作用

死亡受体通过细胞内信号传导途径可诱导细胞凋亡，与机体的生长、发育、病变和死亡有关，本文对新近研究发现的死亡受体的种类、结构特征及其诱导细胞凋亡的机理进行了综述，并讨论了这些死亡受体在肝脏中的生物学和病理生物学作用。     

凋亡网络与缺血性神经元凋亡

近 10年来 ,关于细胞凋亡机制的研究取得了长足的进展 ,在凋亡途径及凋亡调控等方面 ,许多关键性步骤得到了较为明确地阐明。一个由多条细胞凋亡通路交织而成的凋亡网络概貌已经呈现在我们眼前。各种病理生理刺激促进凋亡启动 ,而各个凋亡通路上的一些节点通过负反馈作用抵抗凋亡的发生 ,一旦凋亡刺激超过负反馈所能承担的某一阈值时 ,凋亡信号将突破这一节点继续向下传导 ,并在正反馈作用下逐级放大 ,最终导致细胞凋亡。现就这些研究进展以及缺血性中枢神经元凋亡的特点及抗凋亡治疗的应用作一综述。一、凋亡信号的传导途径凋亡的发生是一…     

线粒体在细胞凋亡中的作用及分子机制

本文综述了线粒体在细胞凋亡的启动和调控方面的最新进展。细胞受凋亡刺激，Bcl-2家族BH3蛋白(Bim，Bad，Bid等)和其他可能的途径将凋亡信号转入线粒体中，与Bcl-2家族凋亡诱导蛋白共同调节，诱导释放线粒体凋亡蛋白细胞色素c、caspase的二级线粒体激活蛋白Smac、凋亡诱导蛋白、内核酸酶G和Omi/HtrA2等，进而通过caspase依赖途径和非依赖途径诱导细胞凋亡。     

死亡受体的信号传导途径及其调节机制

细胞凋亡是多细胞生物保证个体正常发育成熟和维持正常生理过程所必需的。凋亡细胞表面有特定的感应器即死亡受体 ,死亡受体可以接受胞外的死亡信号而激活细胞内的凋亡机制。本文简要综述了死亡受体的信号传导途径及其调节机制的研究进展。死亡受体 CD95、TNFR1和 DR3的信号传导途径相似 ,均有死亡结构域结合蛋白 FADD和死亡效应蛋白 caspase- 8的参与 ,而 DR4和 DR5的信号传导途径研究得不是十分清楚 ,可能存在FADD依赖性和不依赖性两条不同的信号传导途径     

病毒感染与细胞凋亡

细胞凋亡（apoptosis）是在个体发育过程中为维护机体内环境的稳定、调控机体发育、由基因编码的细胞程序性死亡过程，是机体对外界刺激进行的主动应答，贯穿于机体的整个生命活动过程中。细胞凋亡可以自然发生，也可由病毒等外界因素诱导发生。迄今已发现近20种病毒可调节靶细胞凋亡，如HIV-1感染会导致T淋巴细胞、抗原提呈细胞、神经细胞的凋亡，HBV感染引起肝实质细胞和肝癌细胞的凋亡。病毒感染引起细胞凋亡的途径及机制很多，现对其主要途径与机制作一简述。     

神经酰胺:细胞凋亡信号转导的第二信使分子

神经酰胺是细胞凋亡信号调控中的一个第二信使分子,许多应激刺激能激活神经鞘磷脂循环产生神经酰胺诱导多种细胞体系发生凋亡。神经酰胺介导细胞凋亡的机理尚未完全明了,可能是通过多个下游靶分子包括CAPK、CAPP、PKC、SAPK/JNK、CPP32、Bcl-2以及Ras→Racl JNK/p38-K→GADD153信号传导链等作用于不同的信号转导途径而诱导细胞凋亡的。     

力学影响细胞凋亡及其信号转导机制研究进展

力学刺激会影响细胞凋亡的发生,进而影响组织器官结构和功能的变化,从而在机体的生理病理过程中起到重要作用,与很多疾病的发生发展密切相关。近年来力对细胞凋亡影响的信号转导机制逐渐开始受到细胞力学研究者的关注,现阶段部分实验研究结果显示力学刺激的形式、强度以及作用细胞种类的不同都会影响细胞凋亡,作用的过程和结果不尽相同。这一过程中的信号通路及其凋亡相关基因和蛋白的表达错综复杂,其中涉及的具体信号转导机制尚不明确。本文就细胞凋亡的特点、相关的信号通路、不同力学刺激对细胞凋亡的影响以及其信号转导通路的现阶段研究进展展开综述。     

Mitochondria play a role in the development of non-apoptotic programmed cell death of neutrophils induced by ONO-AE-248

We previously reported that ONO-AE-248, a selective EP3 receptor agonist, has been shown to cause neutrophil death without the typical features of apoptosis and necrosis. However, the mechanism of the neutrophil death is unclear. By using Western blotting, flow cytometry （FACS） and confocal laser scanning microscopy （CLSM）, we investigated the cellular signal transduction pathways of the neutrophil death. The research results showed that the neutrophil death induced by ONO-AE-248 did not show the morphologic changes of apoptosis and was not associated with the activity of caspase-3, caspase-8, and phosphorylation of p38-MAPK. However, impairment of mitochondria transmembrane potential has been found during the process of cell death. These findings suggested that ONO-AE-248 induced a non-apoptotic programmed cell death of neutrophils through partially mitochondria signaling transduction pathway. Cellular ＆ Molecular Immunology.     

Physiological roles of ASK1-mediated signal transduction in oxidative stress- and endoplasmic reticulum stress-induced apoptosis: advanced findings from ASK1 knockout mice

Apoptosis, a molecularly regulated form of cell death, is essential for the normal functioning and homeostasis of most multicellular organisms, and can be induced by a range of environmental, physical, and chemical stresses. As the cellular decision to live or to die is made by the coordinated action and balancing of many different pro- and antiapoptotic factors, defects in control of this coordination and balance may contribute to a variety of human diseases, including cancer and autoimmune and neurodegenerative conditions. In recent years, multiple factors associated with the execution of apoptosis, such as caspases and Bcl-2 family members, have been discovered and their complicated signaling and molecular interactions have been demonstrated; however, the precise mechanistic basis for intracellular and/or extracellular stress-induced apoptosis remains to be fully characterized. Protein kinases contribute to regulation of life and death decisions made in response to various stress signals, and the actions of pro- and antiapoptotic factors are often affected by modulation of the phosphorylation status of key elements in the execution of apoptosis. Apoptosis signal-regulating kinase 1 (ASK1) is a member of the mitogen-activated protein (MAP) kinase kinase kinase family, which activates both the MKK4/MKK7-JNK and MKK3/MKK6-p38 MAP kinase pathways and constitutes a pivotal signaling pathway in various types of stress-induced apoptosis. We have recently shown through ASK1 gene ablation in mice that ASK1 plays essential roles in oxidative stress- and endoplasmic reticulum (ER) stress-induced apoptosis. These stresses are closely linked to physiological phenomena in the control of cell fate, and the resultant apoptosis is implicated in the pathophysiology of a broad range of human diseases. This article reviews our new findings on the physiological roles of ASK1-mediated signal transduction in stress responses and the molecular mechanisms by which ASK1 determines cell fate such as survival, differentiation, or apoptosis, with special focus on the regulatory mechanisms of ASK1-mediated apoptosis induced by oxidative stress and ER stress.     

p38丝裂原活化蛋白激酶信号转导通路在紫外线诱导表皮细胞凋亡中的作用

大量流行病学调查及分子生物学实验研究表明：紫外线可通过诱导活性氧及细胞因子产生DNA损伤和基因表达的改变导致细胞凋亡,这个过程非常复杂,有多个信号转导途径参与.由于细胞凋亡与皮肤癌的发生密切相关,近年来UVB诱导表皮细胞凋亡引起了人们广泛的关注.p38丝裂原活化蛋白激酶（p38MAPK）是细胞内重要的信号传导系统之一,参与细胞生长、发育、分化和凋亡等一系列生理、病理过程.p38MAPK可被紫外线激活,并在紫外线诱发的细胞应答过程中发挥重要的作用.     

Tissue specificity of apoptotic signal transduction

Two major apoptotic pathways exist in mammalian cells: the death receptor and mitochondrial pathways. The cross talk between these two pathways is minimal, and they operate basically independent of each other under physiological conditions. Therefore, the tissue specificity of the signal pathway during apoptosis is observed in various tissues and organs. In this article, I demonstrate several examples of apoptosis induced by different signal pathways: apoptosis of human amniotic epithelial cells upon fetal membrane rupture induced by the death receptor pathway, apoptosis of human endometrial cells shed via menstruation and in the selection of B cells in gut-associated lymphoid tissues induced by both the death receptor and mitochondrial pathways, and apoptosis of lovastatin-induced breast cancer cells induced by the mitochondrial pathway.     

JAK/STAT3信号通路调控肿瘤及其相关生物功能的研究进展

JAK/STAT3信号通路是细胞信号通路中重要的信号传导通路之一,通过影响下游多种效应分子的活化状态,对细胞凋亡和增殖起着关键的作用,并且还诱导胚胎发育、肝脏再生、糖酵解和炎性反应、上皮间质转化和血管再生等一系列生物发生过程,与人类肿瘤的发生发展密切相关。     

Programmed necrosis and its role in management of breast cancer

Breast cancer is one of the major causes of cancer related deaths in women worldwide. A major factor responsible for treatment failure in breast cancer is the development of resistance to commonly used chemotherapeutic drugs leading to disease relapse. Several studies have shown dysregulation of molecular machinery of apoptosis, the major programmed cell death pathway in breast malignancies. Thus, there is an unmet need to search for an alternative cell death pathway which can work when apoptosis is compromised. Necroptosis or programmed necrosis is a relatively recently described entity which has attracted attention in this context. Classically, even in physiological conditions necroptosis is found to act if apoptosis is not functional due to some reason. Recently, more and more studies are being conducted in different malignancies to explore the possibility and utility of inducing cell death by necroptosis. The present review describes the key molecular players involved in necroptotic pathway and their status in breast cancer. In addition, the research done to utilize this pathway for treatment of breast cancer has also been highlighted.     

经典Wnt信号通路与神经退行性疾病关系的研究进展

Wnt信号通路调节多种基因的转录,参与调控生物体的生长、发育以及细胞的增殖、分化和凋亡等重要的生理病理过程。在神经退行性疾病中,经典Wnt信号通路发生改变影响神经元的增殖、分化或对神经元产生毒性作用,导致神经元功能损伤。因此,研究经典Wnt信号通路与神经退行性疾病的发病机制及其治疗的关系有重要意义。     

Role of Ras/Raf/MEK/ERK signaling in physiological hematopoiesis and leukemia development

Recent research on hematological malignancies has shown that malignant cells often co-opt physiological pathways to promote their growth and development. Bone marrow homeostasis requires a fine balance between cellular differentiation and self-renewal; cell survival and apoptosis; and cellular proliferation and senescence. The Ras/Raf/MEK/ERK pathway has been shown to be important in regulating these biological functions. Moreover, the Ras/Raf/MEK/ERK pathway has been estimated to be mutated in 30% of all cancers, thus making it the focus of many scientific studies which have lead to a deeper understanding of cancer development and help to elucidate potential weaknesses that can be targeted by pharmacological agents [1]. In this review, we specifically focus on the role of this pathway in physiological hematopoiesis and how augmentation of the pathway may lead to hematopoietic malignancies. We also discuss the challenges and success of targeting this pathway.