光敏色素对植物抗逆反应的调控研究进展

光敏色素是红光和远红光受体,不但在植物光形态建成中扮演着重要的角色,还参与调控植物抗逆信号通路。阐述了光敏色素及其互作的转录因子通过诱导植物激素信号途径调控植物对病原菌、害虫等生物胁迫的反应及作用机制,以及光敏色素调控植物对临近植物的竞争胁迫、干旱、低温、高温等非生物胁迫反应的作用机制研究进展,并讨论与展望了光敏色素研究领域所面临的挑战与发展方向。     

G-蛋白和cGMP在光敏色素介导的尾穗苋苋红素合成中的作用

以尾穗苋幼苗为材料 ,对G 蛋白和cGMP在红光诱导、光敏色素介导的苋红素合成过程中的作用进行了研究 ,结果表明G 蛋白激活剂霍乱毒素可在暗中诱导苋红素合成 ,其抑制剂百日咳毒素则抑制红光诱导的合成 ;cGMP可以在暗中诱导苋红素合成 ,而Genistein抑制红光、CTX及外源cGMP诱导的苋红素合成 ;鸟苷酸环化酶抑制剂LY 835 83可以抑制红光及CTX诱导的苋红素合成 ,却不能抑制由外源cGMP诱导的苋红素合成 .上述结果表明G 蛋白、鸟苷酸环化酶及cGMP可能都参与了苋红素合成过程中红光信号的转导 ,并且红光信号传递链的顺序可能是红光→光敏色素→G 蛋白→鸟苷酸环化酶→cGMP .     

光敏色素光转化生理学特性研究进展(英文)

植物主要光受体光敏色素调节植物的多种光调控,使其作出最适宜的光生长,如:光形态建成.光敏色素接受光信号的生物功能基于其红光吸收型(Pr)和具有生理活性的远红光吸收型(Pfr)之间的光可逆式光转化.依据光生物学的标准该转化过程与光合作用相比是一个低能光反应过程,而且其间产生的中间过渡态和光敏色素的亚库可能反过来影响光转化的过程而最终表现出生理功能.在此,主要综述了近年来运用时间分辨动力学特别是差分荧光和光化学,研究光敏色素及其中间过度态光生物物理和光生物化学特性的若干进展,讨论了光信号转导的原初光反应的机理.     

光敏色素信号传导研究的一项重要结果

光敏色素（phytochrome）控制高等植物的许多分子、细胞及发育反应。尽管对光敏色素分子本身的认识已很深入，然而，其信号传导过程一直是植物发育生物学中悬而未决的问题。不久前，用单细胞测定法鉴定了参与光敏色素信号传导的几种中间体。本文就此进展简要综述。     

不同光敏色素分子的特异感光性

简要综述两种光敏色素（ＰｈｙＡ、ＰｈｙＢ） 的分子特性、感光性及作用模式等方面的研究进展。光敏色素是一种调节植物中许多光反应的色素蛋白复合体。不同光敏色素分子具有特异的感光性。ＰｈｙＡ负责‘甚低辐照反应’和远红光‘高辐照反应’; 而ＰｈｙＢ则调节‘低辐照反应’及红光‘高辐照反应’。另外, 讨论了ＰｈｙＡ和ＰｈｙＢ在光周期感受中的作用。     

裸子植物中光敏色素PHY-PAS1结构域的适应性进化

光敏色素是一类红光／远红光受体,在植物种子萌发到成熟的整个生长发育过程中均起重要的调节作用。光敏色素PHY-PAS1结构域存在于光敏色素基因家族的所有成员中,对调节发色团的光谱特性和光信号转导非常关键。光敏色素基因家族通过基因重复产生,而基因重复可能与物种形成有关。PHYP基因是裸子植物光敏色素基因家族发生第1次重复后产生的,并且以单拷贝形式存在。为了研究不同裸子植物PHYP基因编码蛋白的PHY-PAS1结构域在进化过程中是否受到相同的选择压力以及是否发生了适应性进化,该研究利用分支模型、位点模型以及分支．位点模型对裸子植物31条PHYP基因序列编码蛋白的PHY-PAS1结构域所受到的选择压力进行了分析。结果表明,在由PHY-PAS1结构域序列构建的系统树中,多数分支处于强烈的负选择压力下（ω〈1）：有14个分支处于正选择压力下（ω〉1）,其中13个分支发生在属内种间;与之相比,在较为古老的谱系中相对缺少这种正选择压力。     

高等植物光敏色素的分子结构、生理功能和进化特征

光敏色素是植物感受外界环境变化的最重要光受体之一, 对红光和远红外光非常敏感。本文综述了光敏色素的分子结构、它所包含的结构域和相应功能以及植物各主要类群中光敏色素基因家族的成员组成与进化关系; 重点在分子水平上介绍了光敏色素的生理功能与作用机制。最后, 基于最新的研究进展提出了将来的研究方向。     

高等植物光敏色素的分子结构、生理功能和进化特征

光敏色素是植物感受外界环境变化的最重要光受体之一,对红光和远红外光非常敏感。本文综述了光敏色素的分子结构、它所包含的结构域和相应功能以及植物各主要类群中光敏色素基因家族的成员组成与进化关系;重点在分子水平上介绍了光敏色素的生理功能与作用机制。最后,基于最新的研究进展提出了将来的研究方向。     

光调控植物种子萌发分子机制研究进展

萌发是种子植物进入农业生态系统的重要发育阶段。对于需光类种子,光是调控其萌发最重要的环境信号因子之一,红光促进而远红光抑制种子萌发。光敏色素是调控种子萌发的主要光受体。活化的光敏色素诱导萌发主效抑制因子PIF1发生蛋白降解,调节赤霉素和脱落酸代谢和信号途径相关基因的表达,从而促进种子的萌发。同时,一系列的表观遗传因子通过改变染色质结构,动态调节萌发相关基因的表达从而影响种子的萌发进程。该论文重点论述了光调控种子萌发的转录及表观遗传机制研究进展,并对其在农业生产中的应用进行了展望。     

光色素信号通路中磷酸化修饰研究进展

光是植物的唯一能量来源, 植物在进化过程中产生不同的光敏色素来感知光信号。光信号通路中元件通常被特异翻译后修饰调节。光敏色素是一种自磷酸化的丝氨酸/苏氨酸蛋白激酶, 可以被一些蛋白磷酸酶去磷酸化。通过对光敏色素A (phyA)和光敏色素B (phyB)的自磷酸化位点研究, 发现自磷酸化对光敏色素的功能及其介导的信号通路起着非常重要的作用。光激活的光敏色素诱导光敏色素作用因子(PIF)磷酸化, 这对于PIF的正常降解及光形态建成的起始是必需的。该文主要介绍了光敏色素信号通路磷酸化修饰的最新进展, 以期为深入研究光敏色素信号转导机制提供参考。     

Myelin-associated glycoprotein (Siglec-4) expression is progressively and selectively decreased in the brains of mice lacking complex gangliosides

Myelin-associated glycoprotein (MAG, Siglec-4) is a quantitatively minor membrane component expressed preferentially on the innermost myelin wrap, adjacent to the axon. It stabilizes myelin-axon interactions by binding to complementary ligands on the axolemma. MAG, a member of the Siglec family of sialic acid-binding lectins, binds specifically to gangliosides GD1a and GT1b, which are the major sialoglycoconjugates on mammalian axons. Mice with a disrupted Galgt1 gene lack UDP-GalNAc:GM3/GD3 N-acetylgalactosaminyltransferase (GM2/GD2 synthase) and fail to express complex brain gangliosides, including GD1a and GT1b, instead expressing a comparable amount of the simpler gangliosides GM3, GD3, and O-acetyl-GD3. Galgt1-null mice produce similar amounts of total myelin compared to wild-type mice, but as the mice age, they exhibit axon degeneration and dysmyelination with accompanying motor behavioral deficits. Here we report that Galgt1-null mice display progressive and selective loss of MAG from the brain. At 1.5 months of age, MAG expression was similar in Galgt1-null and wild-type mice. However, by 6 months of age MAG was decreased approximately 60% and at 12 months of age approximately 70% in Galgt1-null mice compared to wild-type littermates. Expression of the major myelin proteins (myelin basic protein and proteolipid protein) was not reduced in Galgt1-null mice compared to wild type. MAG mRNA expression was the same in 12-month-old Galgt1-null compared to wild-type mice, an age at which MAG protein expression was markedly reduced. We conclude that the maintenance of MAG protein levels depends on the presence of complex gangliosides, perhaps due to enhanced stability when MAG on myelin binds to its complementary ligands, GD1a and GT1b, on the apposing axon surface.     

Immune complexes, but not streptococcal cell walls or zymosan, cause chronic arthritis in mouse strains susceptible for collagen type II auto-immune arthritis

In this study we investigated mechanisms involved in the chronic character of experimental collagen type II induced arthritis (CIA). We compared the knee joints of mouse strains which are prone to develop this autoimmune disease (DBA/1,B10RIII) with other nonsusceptible mouse strains (C57Bl/6,BALB/c) in their reaction to different stimuli: immune complexes (IC), zymosan and streptococcal cell walls (SCW). Inflammation was evaluated by(99m)Tc uptake measurements and in haematoxylin- and eosin-stained knee-joint sections. Passively induced immune complex mediated arthritis (ICA) in knee joints of C57Bl/6 and BALB/c mice, showed moderate cell influx at day 3, whereas at day 7 only minor amounts of inflammatory cells were observed. In contrast, in arthritic DBA/1 and, to a lesser extent, in B10.RIII joints, a tremendous cell influx was observed at day 3 and even at day 14 there was still significant synovitis. In contrast, if arthritis was elicited by intra-articular injection of zymosan or SCW in C57Bl/6 and DBA/1, the course of inflammation was similar in both strains and no chronic inflammation developed. In line with severe arthritis, chemotactic factor production was dramatically enhanced in ICA in DBA/1 mice, and a prolonged production of IL-1 was evident. When IL-1 was neutralized before or during the ICA using specific anti-IL-1alpha,beta antibodies, inflammation could be blocked completely. Single or multiple injection of IL-1 in the knee joint of C57Bl/6 or DBA/1 showed comparable inflammation, indicating that the chemotactic response per se is comparable in both strains. No prolonged production of IL-1 was found during zymosan or SCW arthritis. Selective removal of macrophages from the synovial intima prior to ICA induction (using clodronate-containing liposomes) prevented the onset of inflammation in C57Bl/6 and DBA/1 mice. It can be concluded that immune complexes, but not zymosan or SCW, cause a more severe and chronic arthritis in mouse strains which are susceptible for collagen type II autoimmune arthritis. This is due to higher and prolonged expression of IL-1 and chemotactic factors, caused by stimulation with immune complexes. The interaction of IC with lining macrophages probably plays a dominant role in development of chronicity.     

Glutamatergic signaling in cellular transformation

The role of the glutamatergic system in cancer cell homeostasis has expanded exponentially over the last decade. Once thought to participate only in synaptic transmission and neuronal excitability, the presence of functional glutamate receptors has since been demonstrated in peripheral tissues. Most notable is the implication of glutamate receptors in the pathophysiology of various human malignancies. We previously described the oncogenic properties of metabotropic glutamate receptor 1 (Grm1), a G-protein-coupled receptor in melanoma development in vivo. TG-3, a transgenic mouse line, developed spontaneous melanoma with 100% penetrance in the absence of any known stimuli. Stable Grm1-mouse melanocytic clones display transformed phenotypes in vitro and were aggressively tumorigenic in vivo. Recent reports from other groups implicate two additional members of the metabotropic glutamate receptor family in melanomagenesis, overexpression of mGluR5 and activating mutations in GRM3. These findings highlight a previously underappreciated link between the glutamate signaling pathway and oncogenesis in melanoma biology, raising exciting possibilities in elucidating mechanisms in melanocyte transformation and exploring glutamate receptors as novel therapeutic targets. Here we further consider the potential mechanisms by which glutamate receptors can function as an oncogene leading to malignant transformation.     

与线粒体分裂有关的蛋白质研究进展

在活细胞内线粒体处于不断的融合与分裂状态,线粒体融合与分裂的动态平衡影响着线粒体的形态和数量,本文对近年来与线粒体分裂有关的蛋白质研究进行了综述：（1）酵母（S.cerevisae)中的Dnm1蛋白或它的同源蛋白质可能通过缠绕于线粒体的收缩部分而影响线粒体外膜分裂;（2）位于线粒体上的3种同源蛋白Mdv1/Fis2/Gag3与Dnm1能短暂结合,它们都是线粒体分裂装置的组成部分;（3）一个插入线粒体外膜的跨膜蛋白Fisl或Mdv2极有可能是线粒体分裂装置的招募因子,并且由它启动分裂过程;（4）分布于膜间隙（IMS）中的Mgm1蛋白并不负责线粒体内膜分裂,这与以前的观点相反。     

Galectin-1, a cell adhesion modulator, induces apoptosis of rat Leydig cells in vitro

Galectin-1 (Gal-1), a beta galactoside-binding lectin, is involved in multiple biological functions, such as cell adhesion, apoptosis, and metastasis. On the basis of its ability to interact with extracellular matrix (ECM) glycoproteins, we investigated the Gal-1 effect on Leydig cells, which express and are influenced by ECM proteins. In this study, Gal-1 was identified in Leydig cell cultures by immunofluorescence. To gain insight into its biological role, Gal-1 was added to purified rat Leydig cells, under both basal and human chorionic gonadotrophin-stimulated conditions. Substantial morphological changes were observed, and cell viability showed an 80% decrease after 24 h culture. As a functional consequence of Gal-1 addition, testosterone production was reduced in a dose-dependent fashion, reaching a minimum of 26% after 24 h compared with basal values. cAMP showed a similar variation after 3 h. Assessment of DNA hypodiploidy and caspase activity determinations indicated that the reduction in viability and in steroidogenesis was caused by apoptosis induced by Gal-1. Besides, addition of Gal-1 caused Leydig cell detachment. Presence of laminin-1 or lactose prevented the effect of Gal-1, suggesting that the carbohydrate recognition domain is involved in inducing apoptosis. These findings demonstrate a novel mechanism, based on Gal-1 and laminin-1 interaction, which could help us better understand the molecular basis of Leydig cell function and survival control.     

An interluekin 1B allele, which correlates with a high secretor phenotype, is associated with diabetic nephropathy

Induction of interleukin 1 activates vascular endothelial and kidney mesangial cells, and increases production of type IV (basement membrane) collagen. Hence, genes within the interleukin 1 gene cluster are potential candidates in the pathogenesis of diabetic nephropathy. In a previously validated case-control study from Northern Ireland, consisting of 95 patients with insulin-dependent (type 1) diabetes and nephropathy (cases) and 96 patients with insulin-dependent (type 1) diabetes without nephropathy (controls), the authors performed PCR-based genotyping of specific DNA polymorphisms within the interleukin 1A, interleukin 1B, interleukin 1 (type 1) receptor and interleukin 1 receptor antagonist genes. The groups were matched for age at onset and duration of diabetes. A statistically significant increase was found in the allele frequency of the interleukin 1B*2 allele in cases compared to controls (chi2=7. 19, df.=1; P=0.007, Pcorr=0.028). The results of this study suggest that the interleukin 1B*2 allele, or a susceptibility factor in linkage disequilibrium with this allele, is associated with diabetic nephropathy in the Northern Ireland population.     

Regulation of the interleukin-1 receptor antagonist in THP-1 cells by ligands of the peroxisome proliferator-activated receptor gamma

Monocytes/macrophages (Mphi) play a pivotal role in the persistence of chronic inflammation and local tissue destruction in diseases such as rheumatoid arthritis and atherosclerosis. The production by Mphi of cytokines, chemokines, metalloproteinases and their inhibitors is an essential component in this process, which is tightly regulated by multiple factors. The peroxisome proliferator-activated receptors (PPARs) were shown to be involved in modulating inflammation. PPARgamma is activated by a wide variety of ligands such as fatty acids, the anti-diabetic thiazolidinediones (TZDs), and also by certain prostaglandins of which 15-deoxy-Delta(12,14)-PGJ2 (PGJ2). High concentrations of PPARgamma ligands were shown to have anti-inflammatory activities by inhibiting the secretion of interleukin-1 (IL-1), interleukin-6 (IL-6) and tumour necrosis factor alpha (TNFalpha) by stimulated monocytes.The aim of this study was to determine whether PGJ2 and TZDs would also exert an immunomodulatory action through the up-regulation of anti-inflammatory cytokines such as the IL-1 receptor antagonist (IL-1Ra). THP-1 monocytic cells were stimulated with PMA, thereby enhancing the secretion of IL-1, IL-6, TNFalpha, IL-1Ra and metalloproteinases. Addition of PGJ2 had an inhibitory effect on IL-1, IL-6 and TNFalpha secretion, while increasing IL-1Ra production. In contrast, the bona fide PPARgamma ligands (TZDs; rosiglitazone, pioglitazone and troglitazone) barely inhibited proinflammatory cytokines, but strongly enhanced the production of IL-1Ra from PMA-stimulated THP-1 cells. Unstimulated cells did not respond to TZDs in terms of IL-1Ra production, suggesting that in order to be effective, PPAR ligands depend on PMA signalling. Basal levels of PPARgamma are barely detectable in unstimulated THP-1 cells, while stimulation with PMA up-regulates its expression, suggesting that higher levels of PPARgamma expression are necessary for receptor ligand effects to occur. In conclusion, we demonstrate for the first time that TZDs may exert an anti-inflammatory activity by inducing the production of the IL-1Ra.     

ERK1/2和p-ERK1/2在肺癌组织中的表达及意义

目的研究细胞外信号调节激酶1/2（extracellular regulated kinase 1/2,ERK1/2）及其磷酸化状态（p-ERK1/2）在不同分化程度肺癌中的表达情况,探讨二者与肺癌侵袭、转移的关系。方法采用免疫组化（Envision）法,检测79例肺癌组织及l2例癌旁正常肺组织中ERK1/2和p-ERK1/2的表达。结果ERK1/2在高、中、低分化组表达率分别为13.6%,39.4%,66.7%,p-ERK1/2在高、中、低分化组表达率分别14.3%,27.3%,79.2%（P〈0.05）;无淋巴结转移者阳性率为20%,有淋巴结转移者阳性率为50.1%（P〈0.05）。ERK1/2和p-ERK1/2的表达在不同年龄、性别、肿瘤大小、肿瘤病理类型无显著性差异,而与分化程度有关,其中p-ERK1/2的表达还与有无淋巴结转移有关。结论ERK1/2和p-ERK1/2在肺癌组织中高表达且与分化程度有关。     

Interaction of GDP-4-keto-6-deoxymannose-3,5-epimerase-4-reductase with GDP-mannose-4,6-dehydratase stabilizes the enzyme activity for formation of GDP-fucose from GDP-mannose

We cloned the GDP-4-keto-6-deoxymannose-3,5-epimerase-4-reductase gene from Arabidopsis thaliana (AtFX/GER1). The yeast Saccharomyces cerevisiae was transfected with the AtFX/GER1 gene coexpressed with GDP-mannose-4,6-dehydratase gene of A. thaliana (MUR1). In vitro GDP-fucose synthesis activity was observed in the cytoplasmic fraction of cells coexpressing the AtFX/GER1 gene and MUR1 gene. However, the cytoplasmic fraction of cells expressing MUR1 alone did not show the GDP-mannose-4,6-dehydratase activity. This result suggests that the AtFX/GER1 protein may contribute to maintenance of the MUR1 protein as the active form. Immunoprecipitation experiments showed that both proteins interact with each other, indicating that this interaction is required to maintain MUR1 protein as the active or stable form. Finally, in vivo GDP-fucose synthesis activity was analyzed by measuring the amount of GDP-fucose produced in the cytoplasm of yeast cells. The amount of GDP-fucose in cells coexpressing MUR1 and AtFX/GER1 genes was 3.5 times higher than the amount of GDP-mannose in the same cells, indicating that this coexpression system is suitable for production of the valuable sugar nucleotide GDP-fucose in yeast.     

Ran-dependent nuclear export mediators: a structural perspective

Nuclear export is an essential eukaryotic activity. It proceeds through nuclear pore complexes (NPCs) and is mediated by soluble receptors that shuttle between nucleus and cytoplasm. RanGTPase-dependent export mediators (exportins) constitute the largest class of these carriers and are functionally highly versatile. All of these exportins load their substrates in response to RanGTP binding in the nucleus and traverse NPCs as ternary RanGTP-exportin-cargo complexes to the cytoplasm, where GTP hydrolysis leads to export complex disassembly. The different exportins vary greatly in their substrate range. Recent structural studies of both protein- and RNA-specific exporters have illuminated how exportins bind their cargoes, how Ran triggers cargo loading and how export complexes are disassembled in the cytoplasm. Here, we review the current state of knowledge and highlight emerging principles as well as prevailing questions.