溶酶体与细胞凋亡

在特定条件下,包括活性氧、鞘氨醇、细胞凋亡效应因子Bax等在内的多种刺激因子均可诱发溶酶体膜通透,之后溶酶体内含的蛋白酶（如组织蛋白酶等）及其他水解酶从溶酶体释放至胞浆中,通过剪切效应分子、激活包括凋亡酶在内的其他水解酶而启动细胞凋亡程序的执行。简要概括了引发溶酶体膜通透的可能机制及溶酶体参与细胞凋亡的主要途径。     

溶酶体组织蛋白酶B、L和S在糖尿病肾病发生发展中的作用

溶酶体组织蛋白酶(cathepsins, Cats)是一类存在于细胞内和细胞外的具有多种生物活性的蛋白酶,是哺乳动物体内蛋白水解的主要参与者。除了能影响细胞外基质稳态、自噬、细胞凋亡过程外,还对肾小球通透性、内皮功能和炎症具有调节作用。多种Cats表达活性的失调参与急慢性肾脏疾病的发生发展。其中溶酶体组织蛋白酶B(cathepsins B, CatB)、溶酶体组织蛋白酶L(cathepsins L, CatL)及溶酶体组织蛋白酶S(cathepsinsS, CatS)作为糖尿病肾病(diabetic nephropathy, DN)病理生理中的关键参与者受到了广泛的关注。目前,越来越多的证据表明CatB、L和S可能是诊断和治疗DN的新靶点。本文主要对CatB、L及S在DN的作用及相关机制进展进行综述。     

线粒体与细胞凋亡调控

细胞凋亡是一个受到一系列相关基因严格调控的细胞死亡过程。线粒体是细胞凋亡调控的活动中心。在凋亡因子的刺激下,线粒体释放出不同促凋亡因子如细胞色素C、Smac／Diablo等,激活细胞内凋亡蛋白酶Caspase。我们发现,活化后的Caspase可以反过来作用于线粒体,引发更大量线粒体细胞色素c的释放,构成细胞色素c释放的正反馈调节机制,从而导致电子传递链的中断、膜电势的丧失、胞内ROS的升高以及线粒体产生ATP功能的完全丧失。Bcl-2家族蛋白在细胞色素C释放和细胞凋亡调控中起关键作用。     

组织蛋白酶D的功能多样性

组织蛋白酶D（cathepsin D,CTSD）是真核细胞溶酶体中天冬氨酸蛋白酶家族的主要成员,具有非常独特的合成和转运方式.CTSD由粗面内质网合成,通过多种蛋白质水解途径最终抵达细胞内的小泡结构（溶酶体、核内体、吞噬体）,从而发挥其生物学功能.早期认为,CTSD在溶酶体中只参与蛋白质的水解作用.近年研究发现,CTSD在多种生理（细胞增殖、细胞凋亡、细胞衰老和组织内稳态）和病理（阿尔茨海默病、动脉粥样硬化、先天性肌肉萎缩和癌症）条件中均发挥重要作用,并因其生物学功能的多样性而受到广泛关注.本文将着重对CTSD的生物合成与激活、生物学功能及临床应用进行综述,以期为疾病的诊断与治疗、药物的研发与筛选提供前沿的理论依据,为人类健康带来新的希望.     

不同种株利什曼原虫对Balb/c小鼠和金黄地鼠的致病性研究

为了比较不同种株利什曼原虫对实验动物的致病性,分别将5×107的杜氏利什曼原虫SC6株、热带利什曼原虫K27株、婴儿利什曼原虫LEM235株和婴儿利什曼原虫KXG-Liu株前鞭毛体与无鞭毛体感染Balb/c小鼠和金黄地鼠,观察各感染动物皮肤损害状况,3月后,有限稀释培养法分别检测肝和脾脏内的虫荷数.发现不同种株利什曼原虫引起的疾病存在极大的异质性,杜氏利什曼原虫四川SC6株致Balb/c小鼠轻微皮肤损害,肝和脾脏内重度虫荷数,金黄地鼠肝和脾脏内重度虫荷数;热带利什曼原虫K27株致Balb/c小鼠严重的皮肤损害,但肝和脾脏的虫荷数较低,金黄地鼠肝和脾脏中未查见原虫;婴儿利什曼原虫LEM235株致Balb/c小鼠严重的皮肤损害,肝和脾脏内重度虫荷数,金黄地鼠肝和脾脏内重度虫荷数;婴儿利什曼原虫KXG-Liu株可致Balb/c小鼠严重的皮肤损害,肝和脾脏中度虫荷数,金黄地鼠肝和脾脏内少量虫荷数.另外,还发现原虫的生活史状态和进入机体的途径及实验动物的类型对不同种株利什曼原虫感染致病产生影响.     

Caspase的非凋亡性作用CSCD

Caspase是一类胱天蛋白酶家族。大多数Caspase以半胱氨酸作为裂解底物的亲核基团,通过切割底物蛋白引起细胞凋亡。但是,研究发现Caspase存在非凋亡性作用,即Caspase活化后并不引发细胞凋亡,而是通过剪切不同底物或蛋白质互作,介导其他生物学事件,包括细胞增殖、分化、迁移、存活、形态重塑等。部分细胞的分化依赖于Caspase瞬时或位点局限的激活,细胞形态呈现类似于凋亡(不完全凋亡)的改变。Caspase对信号分子、转录因子的剪切灭活,可发挥转换细胞命运和分化进程的作用。在组织损伤时,应激细胞Caspase活化后,可提高自身防御能力,并通过旁分泌来指导邻近细胞进行补偿修复。因此,Caspase的活化不仅仅是一种细胞死亡信号,它的特定活化还是更改细胞形态、行为、命运的重要应激信号和效应分子。     

Caspase的非凋亡性作用

Caspase是一类胱天蛋白酶家族。大多数Caspase以半胱氨酸作为裂解底物的亲核基团,通过切割底物蛋白引起细胞凋亡。但是,研究发现Caspase存在非凋亡性作用,即Caspase活化后并不引发细胞凋亡,而是通过剪切不同底物或蛋白质互作,介导其他生物学事件,包括细胞增殖、分化、迁移、存活、形态重塑等。部分细胞的分化依赖于Caspase瞬时或位点局限的激活,细胞形态呈现类似于凋亡(不完全凋亡)的改变。Caspase对信号分子、转录因子的剪切灭活,可发挥转换细胞命运和分化进程的作用。在组织损伤时,应激细胞Caspase活化后,可提高自身防御能力,并通过旁分泌来指导邻近细胞进行补偿修复。因此,Caspase的活化不仅仅是一种细胞死亡信号,它的特定活化还是更改细胞形态、行为、命运的重要应激信号和效应分子。     

Ca~(2+)信号调控细胞死亡的亚细胞和分子机制

Ca2+在细胞死亡过程中起至关重要的作用。胞浆和/或线粒体(MT)内Ca2+超载不但是多种原因、多种方式细胞死亡的起始因素,也可通过激活蛋白酶、核酸酶、磷脂酶等酶,直接或间接通过与Bcl-2家族蛋白等重要调节因素的相互作用,全程参与死亡生化反应。内质网(ER)释放Ca2+与MT、溶酶体(LS)、细胞核相互作用,激活多种细胞死亡信号转导通路,导致细胞凋亡、坏死和自噬性细胞死亡。本文重点介绍Ca2+信号在亚细胞和分子水平调控细胞死亡的机制研究方面的最新进展。     

MFN1介导的线粒体融合在心肌细胞凋亡中的作用研究

目的:探讨线粒体融合关键蛋白MFN1介导的线粒体融合在调控心肌细胞凋亡中的作用。方法:通过si RNA降低体外培养H9C2心肌细胞中MFN1的表达后,采用Western blot检测线粒体细胞色素c(Cyto c)释放及其下游凋亡效应分子Caspase9与Caspase3活性,流式细胞术检测细胞内活性氧(ROS)的产生情况,流式细胞术检测细胞凋亡的情况。结果:干扰MFN1可显著促进H9C2心肌细胞内细胞色素c由线粒体释放至胞浆,促进Caspase9与Caspase3的激活,增加细胞内活性氧ROS产生并提高细胞凋亡率(均P0.05)。结论:MFN1介导的线粒体融合可保护心肌细胞凋亡,其机制可能与抑制ROS产生与细胞色素C释放有关。     

细胞死亡的新理论：溶酶体线粒体轴理论

线粒体在细胞死亡中占有中心地位,但其他细胞器影响线粒体启动细胞死亡的机制仍不十分明确. 近几年来,随着对溶酶体功能的不断了解,Alexei等提出了溶酶体线粒体轴理论.这一理论阐述了溶酶体与线粒体的相互作用,并最终导致细胞死亡的机理. 各种致凋亡因素作用于溶酶体,导致溶酶体膜通透性改变．溶酶体膜通透性改变能通过铁依赖的方式、脂褐素相关的方式、Bcl-2家族依赖的方式和Rho/ROCK途径-JNK信号通路的方式影响线粒体,造成线粒体膜通透性改变,进而启动细胞死亡．而线粒体膜通透性改变能通过ROS依赖的方式和Bcl-2家族依赖的方式引起溶酶体通透性改变,最终导致细胞死亡. 溶酶体线粒体轴理论还能用于解释非酒精性脂肪肝和溶酶体贮积症的发病机制．本文将对溶酶体线粒体轴理论及其与疾病的关系两方面进行阐述．     

Recent advances in the study of Kaposi's sarcoma-associated herpesvirus replication and pathogenesis

It has now been over twenty years since a novel herpesviral genome was identified in Kaposi's sarcoma biopsies. Since then, the cumulative research effort by molecular biologists, virologists, clinicians, and epidemiologists alike has led to the extensive characterization of this tumor virus, Kaposi's sarcoma-associated herpesvirus(KSHV; also known as human herpesvirus 8(HHV-8)), and its associated diseases. Here we review the current knowledge of KSHV biology and pathogenesis, with a particular emphasis on new and exciting advances in the field of epigenetics. We also discuss the development and practicality of various cell culture and animal model systems to study KSHV replication and pathogenesis.     

The structure, reproduction and taxonomy of Vidalia and Osmundaria (Rhodophyta, Rhodomelaceae)

Comprises species occurring mostly in subtidal habitats in tropical, subtropical and warm-temperate areas of the world. An analysis of the type species, V. spiralis (Sonder) Lamouroux ex J. Agardh, a species from Australia, establishes basic characters for distinguishing species in the genus. These characters are (1) branching patterns of thalli, (2) flat blades that may be spiralled on their axis, (3) width of the blade, (4) primary or secondary derivation of sterile and fertile branchlets and (5) position of sterile and fertile branchlets on the thalli. Application of the latter two characters provides an important basic method for separation of species into three major groups. Osmundaria , a genus known only in southern Australia, was studied in relation to Vidalia , and its separation from the Vidalia assemblage is not accepted. Species of Vidalia therefore are transferred to the older genus name, Osmundaria. Two new species, Osmundaria papenfussii and Osmundaria oliveae are described from Natal. Confusion in the usage of the epithet, Vidalia fimbriala Brown ex Turner has been clarified, and Vidalia gregaria Falkenberg, described as an epiphyte on Osmundaria pro/ifera Lamouroux, is revealed to be young branches of the host, Osmundaria prolifera.     

New or rare chromosome counts in Artemisia L. (Asteraceae, Anthemideae) and related genera from Kazakhstan

Fifteen chromosome counts of six Artemisia taxa and one species of each of the genera Brachanthemum, Hippolytia, Kaschgaria, Lepidolopsis and Turaniphytum are reported from Kazakhstan. Three of them are new reports, two are not consistent with previous counts and the remainder are confirmations of very scarce (one to four) earlier records. All the populations studied have the same basic chromosome number, x = 9, with ploidy levels ranging from 2x to 6x. Some correlations between ploidy level, morphological characters and distribution are noted.     

肝癌中HBV和HCV基因和抗原的分布及意义

采用原位分子杂交方法检测HCV RNA及HBV X基因;采用免疫组织化学方法研究HCV核心抗原,非结构区C33c抗原及HBxAg在肝细胞肝癌中的定位及分布.结果表明(1)HCV RNA、HBV X基因在肝细胞肝癌组织检出率分别为40%(55/136)和82%(112/136).HCV RNA定位于癌细胞的胞浆内,阳性细胞呈散在、灶状及弥漫分布三种形式;HBV X基因在肝癌细胞中的分布呈胞浆型、核型及核浆型,阳性细胞也呈上述三种分布形式;(2)HCV C33c抗原、核心抗原在肝细胞肝癌中的阳性率为81%(133/164)及86%(141/164).C33c抗原定位于癌细胞及肝细胞的胞浆内;核心抗原既定位于癌细胞核中,又可定位于胞浆中.C33c抗原阳性细胞以灶状分布为主;而核心抗原阳性细     

Selection with two alleles and complete dominance

For a plant selection model with frequency-independent viabilities, fertilities and selfing rates, it is shown that apart from global fixation, for certain parameter combinations a protected polymorphism and facultative fixation (either allele may become fixed according to initial frequencies) may both occur. Facultative fixation requires different selling rates for the dominant and recessive type. Protection of the polymorphism requires resource allocation for male and female function. In this connection the problem of purely genetically caused population extinction is discussed.
For general frequency dependence and regular segregation, the chances for establishment of a completely recessive gene are compared to those of a completely dominant gene. It is proven that the process of establishment of the recessive gene, despite a fitness advantage, may be considerably endangered by drift effects if random mating prevails. The recessive gene may reach the same effectivity in establishment as a dominant gene, only if the recessive homozygote mates exclusively with its own type during the period of establishment.