骨桥蛋白对细胞生存的多重作用

骨桥蛋白(osteopontin, OPN)作为一种分泌性蛋白质广泛存在于多种组织细胞中,不仅调控肿瘤细胞的转移、侵袭和增殖,也在炎症反应、血管再生等生理过程中发挥作用。OPN通过与受体结合直接或间接地激活细胞内信号途径,介导细胞与细胞、细胞与细胞外基质之间的相互作用,从而参与调控细胞的生存。大量实验证实,OPN能够促进细胞的增殖,抑制细胞凋亡,尤其是对于肿瘤细胞。但在有些细胞中,OPN对细胞命运的影响却恰恰相反。本文综述了OPN在不同条件下对细胞存活、活化和增殖,细胞自噬和细胞凋亡的多重作用及其作用途径,为进一步研究OPN对不同细胞作用的受体及其信号网络机制提供重要理论基础。     

PIAS蛋白家族的研究进展

PIAS(protein inhibitor of activated STAT)蛋白家族是一种能够激活STAT转录活性的抑制蛋白,共包括4个成员,可与多种蛋白发生相互作用,从而影响靶蛋白的活性和功能,其主要与STAT、Wnt、TGF-β、NF-κB等通路的转录因子或转录辅因子相互作用以调控下游基因的转录活性。在细胞周期中,PIAS蛋白是细胞衰老和细胞凋亡的调节子,可促进细胞的扩散和衰老。在肿瘤发生中,PIAS蛋白的过表达能抑制癌细胞的增殖并诱导其凋亡。除此之外,在生殖系统和神经系统中,PIAS家族蛋白也能通过与相关的转录因子或激素受体相互作用影响其发生发展的过程。     

BAG-1蛋白及其对神经系统疾病调控研究进展

B细胞CLL/淋巴瘤2关联凋亡基因1（B-cell CLL/lymphoma 2-associated athanogene-1,BAG-1）编码的蛋白是一种多功能结合蛋白,包含不同功能的结构域,可与抗凋亡蛋白（Bcl-2）、热激蛋白70（heat shock protein 70,Hsp70/Hsc70）、细胞转化分裂介质（Raf-1）、类固醇激素受体和DNA等结合,对于调节细胞凋亡、信号传导、基因转录、细胞增殖与分化等具有重要作用。BAG-1参与多种神经系统疾病（如阿尔茨海默病、帕金森氏病、亨廷顿舞蹈病、脑中风、脊髓损伤以及神经精神障碍疾病）的发生发展过程。主要就BAG-1的结构、功能及其对神经系统疾病影响的研究进展进行了综述,以期为神经系统疾病的研究和治疗提供参考。     

The endothelin axis in uterine leiomyomas: new insights

The endothelin axis, comprising endothelin-1 (ET-1) and its receptors (ETA and ETB), is involved in the pathophysiology of different human tumors. Here we review conventional approaches and gene expression profiling indicating the association of ET-1 and its cognate receptors with human and rat leiomyomas, the most common benign tumors of myometrium. Specifically, ET-1/ETA interactions affect human and rat leiomyoma cell proliferation through protein kinase C and mitogen-activated protein kinase-dependent signaling pathways. Recent experiments demonstrate that the ET-1 axis exerts a potent antiapoptotic effect involving sphingolipid metabolism and prostaglandin-endoperoxide synthase 2/prostaglandin system in the rat Eker leiomyoma tumor-derived ELT3 cell line. Evidence supports that steroid hormones, growth factors, and extracellular matrix are key regulators of the leiomyoma growth. Interestingly, the ET-1 axis is under steroid hormones and can cooperate with these growth factors. Therefore, ET-1 alone or in association with these factors could contribute to the complex regulation of uterine tumor growth, such as proliferation, survival, and extracellular matrix production. This review summarizes current knowledge and emerging data on ET-1 in uterine leiomyoma pathology.     

甾体激素受体功能特异性的结构基础

甾体激素受体家族包括雌激素受体、雄激素受体等五个亚家族,在机体组织细胞的生长分化、发育生殖、内环境稳定等几乎所有生理过程中都起着重要的作用。研究甾体激素受体亚家族的特异性可以加深对该家族功能的理解,并且具有潜在的临床应用价值。采用进化踪迹方法对该家族的配体结合域（LBD）进行分析,探讨了决定亚家族功能特异性的结构基础。结果表明,甾体激素受体的各亚家族可能同相应的内源性配体存在着共进化关系;配体结合处的踪迹残基决定了受体－配体间的氢键作用和疏水相互作用模式并导致了亚家族的配体结合特异性。上述结论可用于甾体激素受体的配体结合特异性的改造以及新型组织选择性配体（如选择性雌激素受体调节剂,SERM）的设计。     

类胡萝卜素的抗癌作用与基因表达的联系

类胡萝卜素是通过干扰癌细胞生长或细胞死亡的有关途径显示其抗癌作用的,包括细胞增殖、生长因子的信号传输、细胞间隙连接通讯、细胞分化及凋亡。类胡萝卜素引起参与这些过程的调节蛋白质表达发生改变。已发现几个转录系统在其抗癌活性中起作用,如类视黄素受体、过氧化物酶体激活受体(PPAR)、抗氧化剂应答元件(ARE)、异生素受体及激活剂蛋白-1(AP-1),它们构成各种类胡萝卜素与其它微量营养素协同抗癌作用的基础。     

核孤儿受体TR3/nur77与一种新细胞凋亡机制

核孤儿受体TR3/nur77是一种立刻早期基因（immediate-early gene）的产物,与固醇类激素受体结构相似,是核受体超家族的重要成员之一,可被多种生长因子或凋亡诱导剂诱导表达,具有复杂的生物学功能,涉及细胞增殖、分化发育和凋亡过程.最近对其诱导凋亡机制的研究取得了重大进展,发现当细胞受到凋亡诱导剂刺激后,TR3基因表达升高,其产物从细胞核移位至线粒体膜,引起细胞色素c释放,从而导致细胞凋亡.即TR3的转录激活功能和诱导凋亡功能是由其不同的亚细胞定位结合所决定的,其诱导凋亡过程与其对基因的反式激活功能无关.核转录因子p53也具有类似情况.这种核转录因子由细胞核移位至细胞浆并发挥生物学功能的调控方式是一种新模式,可能具有重要的生物学意义.     

Vitamin D affects proliferation of a murine T helper cell clone

1,25-Dihydroxyvitamin D3 (1,25(OH)2D3), the biologically active form of vitamin D3, has been shown to inhibit the activation of T cell hybridomas and heterogeneous populations of mononuclear leukocytes. Because the response of various clones to 1,25(OH)2D3 may differ, we have examined the proliferative effects of the steroid on an antigen-specific cloned, nontransformed T helper cell line (D10.G4.1 [D10 cells]), and find that in contrast to these previous studies, the steroid is a potent stimulator of lectin-induced proliferation. In these experiments, D10 cells were incubated with concanavalin A and 1,25(OH)2D3, and although the lectin or steroid alone has minimal proliferative effects, their co-addition prompts up to a 50-fold increase in 3H-TdR incorporation at a concentration of 2.5 to 5 X 10(-9) M 1,25(OH)2D3, with significant mitogenesis occurring at 0.1 to 0.3 X 10(-9) M 1,25(OH)2D3. 25-Hydroxyvitamin D3 and 24,25(OH)2D3 have similar activity, but at concentrations two to three times greater than that of 1,25(OH)2D3, reflecting their relative affinities for the 1,25(OH)2D3 receptor. In addition, lectin treatment enhances 1,25(OH)2D3 receptor capacity fourfold to fivefold, an event coupled with the appearance of positive cooperativity. Although the steroid does not affect the quantity of bioassayable T cell growth factors as assessed by HT-2 cell proliferation, the expression of immunoreactive IL 2 receptors by lectin-activated D10 cells exposed to 1,25(OH)2D3 is enhanced. In contrast to its proliferative effect in the absence of IL 1, 1,25(OH)2D3 exerts biphasic effects on D10 replication when this monokine is present. Specifically, this steroid augments D10 proliferation at low concentrations of recombinant IL 1, but as the abundance of the monokine increases in the presence of 10(-10) to 10(-8) M 1,25(OH)2D3, the peak response of D10 cells to optimal IL 1 concentrations is diminished. Therefore, in this clone, 1,25(OH)2D3 presents itself as a regulator of T helper cell proliferation.