细胞凋亡的线粒体途径调控

细胞凋亡是近年来研究的一个热点问题，涉及到细胞内许多复杂的生化过程．线粒体是真核生物能量和代谢的中心，也是细胞凋亡信号传导途径中起关键调节作用的细胞器，对细胞凋亡的线粒体途径调控机制进行研究具有重要意义．本文综述了细胞凋亡过程中线粒体途径的信号传导及其调控机制、线粒体对细胞凋亡信号的反应、细胞凋亡过程中线粒体功能丧失几方面的研究进展．图1参43     

Raw single-walled carbon nanotube-induced cytotoxic effects in human bronchial epithelial cells: comparison to asbestos

Single-walled carbon nanotubes (SWCNT) are being developed to be used in many industrial and biomedical applications. However, SWCNT's durability and likely fibrous morphology have raised health concerns. The present investigations were focused on understanding the cellular and molecular mechanisms induced by raw SWCNT (SWCNT) in human bronchial-epithelial cells (BEAS-2B). Asbestos (crocidolite) was used as a positive control. Exposure of BEAS-2B cells to SWCNT induced apoptosis, DNA damage, and oxidative stress. The generation of hydroxyl radical (^?OH) and increase of superoxide dismutase (SOD) activity were concentration-dependent. The increase in apoptosis was associated with activation of caspase-3, caspase-7, and poly (ADP-ribose) polymerase-1 (PARP-1). A short recovery period of 6?h of cells from SWCNT exposure resulted in reversal of caspase-3 and caspase-7, and a partial reversal of PARP-1 activation. The activation of PARP-1, caspase-3, and caspase-7 was only partially diminished after a recovery of 6?h from the exposure to crocidolite. Exposure of BEAS-2B cells to SWCNT resulted in the phosphorylation of protein p42/44 (p42/44) and protein p38 (p38). SWCNT did not induce protein serine-threonine kinase (AKT) phosphorylation. For all the above end points, crocidolite induced a greater response compared to SWCNT. SWCNT induced a significant activation of activator protein-1 (AP-1) and nuclear factor kappa B (NF-κB), and the effect was inhibited by mitogen-activated protein kinase (MAPK) inhibitors. SWCNT also induced significant increase in the expression levels of c-Jun, βIGH3, and CD44 genes. The results of this study show that the molecular mechanism for raw SWCNT-mediated toxicity in BEAS-2B cells is through the activation of caspase-3, caspase-7, and PARP-1. Furthermore, the mechanism of AP-1 and NF-κB activation is through MAPK. This bioactivity of raw SWCNT is associated with the generation of oxidative stress and DNA damage. Considering the role of airway epithelium as a critical barrier for normal pulmonary function and focal point for tumor development, this study demonstrates that raw SWCNT activate molecular events which may be linked to adverse biological responses implicated in pulmonary diseases.     

[C8mim]Cl对HepG2细胞凋亡和内质网应激通路的影响

为研究离子液体氯化1-辛基-3-甲基咪唑（[C₈mim]Cl）是否通过内质网应激（ERS）通路诱导细胞凋亡,在MTT法检测细胞活力的基础上,用0,50,100,200μmol/L[C₈mim]Cl处理HepG2细胞24h后,采用流式细胞仪检测细胞凋亡,western blot检测ERS通路相关蛋白表达.结果显示：[C₈mim]Cl处理后HepG2细胞凋亡呈浓度依赖性增高.ERS相关蛋白葡萄糖调节蛋白78（GRP78）、磷酸化RNA依赖的蛋白激酶样内质网激酶（p-PERK）、磷酸化真核起始因子2α（p-eIF2α）、磷酸化肌醇需求酶-1（p-IRE1）、激活转录因子4（ATF4）和ATF6显著上调.[C₈mim]Cl还显著诱导了C/EBP同源蛋白（CHOP）和半胱氨酸天冬氨酸蛋白酶4（caspase 4）蛋白表达,促进了caspase 9和caspase 3活性升高.因此,[C₈mim]Cl可通过ERS通路诱导HepG2细胞凋亡.     

浮游植物程序性细胞死亡研究进展

浮游植物是水生生态系统的基础,在生物地化循环中起着非常重要的作用,浮游植物的死亡势必引起水生生态系统的改变。近年来的研究表明,浮游植物的死亡是浮游植物水华衰退的一个重要原因。浮游植物中是否存在与后生动物类似的程序性细胞死亡（Programmed cell death,PCD）途径,也因此成了一个热点问题。文章对近年来浮游植物死亡表型、PCD生化证据、诱发条件、分子基础方面研究进行了总结。大量证据表明,浮游植物中存在类似细胞凋亡、类凋亡、自噬等途径的PCD,但Caspase基因除具有死亡执行者功能外,还可能具有看家功能。活性氧（ROS）和一氧化氮（NO）在浮游植物PCD过程中可能起到死亡信号分子的作用。部分浮游植物的PCD可以改善种群生存,但其生态学意义总体而言仍存在许多争论。     

浮游植物细胞程序化死亡研究进展

过去,动物摄食和沉降被认为是浮游植物死亡的原因。后来人们发现病毒感染以及逆境条件下的主动死亡(或程序化死亡),也是引起浮游植物死亡的重要原因。文章介绍了浮游植物存在细胞程序化死亡的实验证据和半胱氨酰天冬氨酸特异蛋白酶(caspase)在浮游植物细胞程序化死亡中可能起的作用及浮游植物基因组中的caspase直系同源物。程序化死亡是细胞自主死亡的过程,具有坏死的形态和生物化学过程。浮游植物具有一套后生动物caspase的直系同源物蛋白。作者构建了东海原甲藻cDNA文库,其中有两组EST分别与两个细胞程序化死亡的关键蛋白同源,它们分别是半胱氨酰天冬氨酸特异蛋白酶和分裂细胞核抗体。因此作者推断东海原甲藻可能存在细胞程序化死亡过程。尽管已从细胞生物学特征角度,获得了真核微藻程序化死亡的证据,并从基因组序列中预测出和大规模表达序列标签中鉴定出细胞程序化死亡相关蛋白的编码基因,但离全面认识单细胞真核浮游藻程序化死亡的分子机制以及其生态学意义相差甚远。