硫化氢神经生物学作用的研究进展

硫化氢(hydrogen sulfide,H_2S)作为继一氧化碳、一氧化氮后的第三种新型气体信号分子,得到了研究者们的广泛关注。H_2S在生物机体内发挥了重要的神经生物学作用。本综述主要总结H_2S的神经保护作用和神经调质功能及其机制,并介绍近几年人们对H_2S在神经系统疾病中的作用的研究进展。     

Purinergic mechanisms in the control of gastrointestinal motility

For many years, ATP and adenosine have been implicated in movement regulation of the gastrointestinal tract. They act through three major receptor subtypes: adenosine or P1 receptors, P2X receptors and P2Y receptors. Each of these major receptor types can be subdivided into several different classes and is widely distributed amongst various neurons, muscle types, glia and interstitial cells that regulate intestinal functions. Several key roles for the different receptors and their endogenous ligands have been identified in physiological and pharmacological studies. For example, adenosine acting at A(1) receptors appears to inhibit intestinal motility in various pathological conditions. Similarly, ATP acting at P2Y receptors is an important component of inhibitory neuromuscular transmission, acting as a cotransmitter with nitric oxide. ATP acting at P2X and P2Y(1) receptors is important for synaptic transmission in simple descending excitatory and inhibitory reflex pathways. Some P2Y receptor subtypes prefer uridine nucleotides over purine nucleotides. Thus, roles for UTP and UDP as enteric transmitters in place of ATP cannot be excluded. ATP also appears to be important for sensory transduction, especially in chemosensitive pathways that initiate local inhibitory reflexes. Despite this evidence, data are lacking about the roles of either adenosine or ATP in more complex motility patterns such as segmentation or the interdigestive migrating motor complex. Clarification of roles for purinergic transmission in these common, but understudied, motility patterns will depend on the use of subtype-specific antagonists that in some cases have not yet been developed.     

New Talents for an Old Acquaintance: the SR Protein Splicing Factor ASF/SF2 Functions in the Maintenance of Genome Stability

ASF/SF2 is a well-studied SR protein that plays important roles in pre-mRNA splicing and other aspects of RNA metabolism. Genetic inactivation experiments have revealed the fundamental roles of ASF/SF2 and other SR proteins in cell viability and animal development. However, the nature of the events triggered by in vivo depletion of ASF/SF2 remained largely elusive. Recently, we have demonstrated a significant function of ASF/SF2 in the maintenance of genome stability by preventing the formation of R loops, which provided new insights into the essential roles of ASF/SF2 in cellular physiology.     

Some examples of the functions of metal ions in biology

The ways in which certain inorganic elements are used in essential roles within biological systems generally are described. The two roles stressed are (1) electrolytic charge movements and (2) electronic charge movement. The value of helical proteins inside and outside membranes as mechanical coupling devices is analysed.     

Evaluation of the Specific Roles of Anions in Electron Transport and Energy Transfer Reactions in Photosynthesis

Ionic environment is important in regulating photosynthetic reactions. The roles of cations, Mn²⁺, Mg²⁺, Ca²⁺, Na⁺, and K⁺ as cofactors in electron transport, energy transfer, phosphorylation, and carbon assimilation are better known than the roles of anions, except for chloride and bicarbonate. Only a limited information exists on the roles and effects of nitri formate, sulphate, and phosphate. In this review, we evaluate and highlight the roles of some specific anions on electron transport as well as on excitation energy transfer processes in photosynthesis. Anions exert significant effects on thyla membrane conformation and membrane fluidity, possibly by redistributing the thylakoid membrane surface charges. The anion/cation induced phase transitions in the hydrophilic domains of the thylakoid membranes are probably responsible for the various structural and co-related functional changes under stress. Anions are also important in regulation of energy distribution between the two photosystems. Anions do not only divert more energy from photosystem (PS) 2 to PS1, but can also reverse the effect of cations on energy distribution in a valence-dependent manner. Anions affect also the structure of the photosynthetic apparatus and excitation energy distribution between the two photosystems.     

On the role of calcium in the adhesion of embryonic sea urchin cells

Calcium is shown to have several roles in the adhesion of embryonic sea urchin cells. Using an assay that subdivides a cell interaction into sequential steps it is shown that Ca2+ has distinct roles in at least two separate steps. The initial binding step between blastomeres is Ca2+-sensitive, and is shown to require divalent cations themselves rather than replacement of a macromolecular material that might be removed in the absence of Ca2+. The secondary steps of adhesion involve a strengthening of the initial contacts. Ca2+ is shown to be required for at least one and probably more than one of these steps. In addition, the extracellular matrix molecule called hyalin is known to be sensitive to Ca2+ for its polymerization. Hyalin may be involved in the initial steps of cell binding measured by the assay in that cell-cell binding is partially blocked by a Fab antibody fragment directed against hyalin. Finally, two extracts, known from other studies to enhance cell aggregation, were examined for their possible relationship to the Ca2+-sensitive binding of cells. A butanol extract was shown to enhance initial binding in a Ca2+-independent manner. Cells extracted with butanol were greatly reduced in adhesiveness even in the presence of Ca2+. The second extract was obtained from cells by treatment of embryos with divalent cation-free saline. This Ca2+-sensitive factor is shown to contain hyalin which may account for some of its observed activity, though not necessarily all of it. Divalent cation-free-extracted cells regain full adhesiveness immediately upon restoration of Ca2+. Thus the extract is not essential for cell adhesiveness. Together these data show that divalent cations have several roles in the multistepped process called adhesion.     

植物MYB类转录因子研究进展

植物MYB转录因子以含有保守的MYB结构域为共同特征,广泛参与植物发育和代谢的调节。含单一MYB结构域的MYB转录因子在维持染色体结构和转录调节上发挥着重要作用,是MYB转录因子家族中较为特殊的一类。含两个MYB结构域的MYB转录因子成员众多,在植物体内主要参与次一代谢的调节和控制细胞的形态发生。含3个MYB结构域的MYB蛋白与c-MYB蛋白高度同源,可能在调节细胞周期中起作用。     

Hippo信号通路调控免疫细胞的功能

Hippo信号通路最初是在果蝇(Drosophila)中被发现的,是在进化上高度保守并能调控器官大小的信号转导通路。在哺乳动物多种组织器官中,Hippo信号通路的关键激酶MST1和MST2(果蝇Hippo激酶的同源分子)通过抑制下游的转录共激活分子YAP(果蝇中为Yorki)的活性来实现对细胞增殖和凋亡的调控。在这些组织器官中条件性敲除Mst1和Mst2或过表达Yap大都会造成细胞过度增殖或肿瘤的发生。近年来,随着研究的不断深入,Hippo信号通路不依赖于YAP的非经典功能也逐渐被发现。其中,Hippo信号通路多个成员在免疫系统中的调控功能逐渐成为该领域的研究热点,特别是在免疫细胞发育分化、机体自身免疫性疾病及应对病毒和细菌入侵等过程中所发挥的调控作用。本文重点阐述了Hippo信号通路在T淋巴细胞中发育、分化、活化和迁移等方面及在部分天然免疫细胞抗感染过程中的功能和调控。     

Role of the calcium toolkit in cancer stem cells

Cancer stem cells are a subpopulation of tumor cells that proliferate, self-renew and produce more differentiated tumoral cells building-up the tumor. Responsible for the sustained growth of malignant tumors, cancer stem cells are proposed to play significant roles in cancer resistance to standard treatment and in tumor recurrence. Among the mechanisms dysregulated in neoplasms, those related to Ca²⁺ play significant roles in various aspects of cancers. Ca²⁺ is a ubiquitous second messenger whose fluctuations of its intracellular concentrations are tightly controlled by channels, pumps, exchangers and Ca²⁺ binding proteins. These components support the genesis of Ca²⁺ signals with specific spatio-temporal characteristics that define the cell response. Being involved in the coupling of extracellular events with intracellular responses, the Ca²⁺ toolkit is often hijacked by cancer cells to promote notably their proliferation and invasion. Growing evidence obtained during the last decade pointed to a role of Ca²⁺ handling and mishandling in cancer stem cells. In this review, after a general overview of the concept of cancer stem cells we analyse and discuss the studies and current knowledge regarding the complex roles of Ca²⁺ toolkit and signaling in these cells. We highlight that numbers of Ca²⁺ signaling actors promote cancer stem cell state and are associated with cell resistance to current cancer treatments and thus may represent promising targets for potential clinical applications.     

SNHG1 represses the anti-cancer roles of baicalein in cervical cancer through regulating miR-3127-5p/FZD4/Wnt/β-catenin signaling

As a flavonoid, baicalein exhibits remarkable anti-cancer roles in several cancers. However, the factors regulating the antitumorigenic roles of baicalein in cervical cancer remain undefined. Here, we revealed that long noncoding RNA SNHG1 is implicated in the tumor-suppressive roles of baicalein. Functional assays demonstrated that ectopic expression of SNHG1 attenuates the roles of baicalein in repressing cervical cancer cell viability, inducing apoptosis, and repressing migration. SNHG1 silencing promotes the tumor-suppressive roles of baicalein in cervical cancer cell viability, apoptosis, and migration. Xenograft assays showed that SNHG1 reverses the tumor-suppressive roles of baicalein in repressing cervical cancer growth in vivo. Mechanistic investigations revealed that SNHG1 directly binds miR-3127-5p and up-regulates FZD4, a target of miR-3127-5p. Via regulating miR-3127-5p/FZD4, SNHG1 activates Wnt/β-catenin signaling. Moreover, SNHG1 reverses the repressive role of baicalein on Wnt/β-catenin signaling. The effect of SNHG1 on the antitumorigenic process of baicalein was abolished by Wnt/β-catenin signaling inhibitor ICG-001. Together, our observations demonstrated that SNHG1 represses the tumor-suppressive roles of baicalein in cervical cancer through regulating miR-3127-5p/FZD4/Wnt/β-catenin axis, and suggested that targeting SNHG1 represents a potential strategy to enhance the tumor-suppressive roles of baicalein in cervical cancer.Impact statementBaicalein exhibits anti-cancer roles in several cancers. However, the factors influencing the antitumorigenic efficiencies of baicalein in CC remain largely unclear. Here, we provide convincing evidences that lncRNA SNHG1 attenuates the tumor-suppressive roles of baicalein in CC cell viability, apoptosis, migration, and CC tumor growth. This study further demonstrates that the influences of SNHG1 in the antitumorigenic process of baicalein are achieved through modulating the miR-3127-5p/FZD4Wnt/β-catenin axis. SNHG1 attenuates the repressive role of baicalein on Wnt/β-catenin. Therefore, SNHG1 is a novel modulator of the tumor-suppressive roles of baicalein and SNHG1 represents a therapeutic intervention target to reinforce the tumor-suppressive roles of baicalein in CC.     

拟南芥R2R3-MYB类转录因子在环境胁迫中的作用

MYB转录因子是植物转录因子中最大的家族之一,以含有保守的MYB结构域为共同特征,分为三个亚族（R1／2-MYB、R2R3-MYB和R1R2R3-MYB）,其中含有两个MYB结构域的R2R3-MYB成员最多,广泛参与植物次生代谢调控、细胞形态发生、胁迫应答、分生组织形成及细胞周期控制等。近年来,R2R3-MYB在植物逆境胁迫中的作用引起了广泛关注,本文综述了拟南芥R2R3-MYB蛋白在环境胁迫响应中作用的研究进展。     

Roles of the EZH2 histone methyltransferase in cancer epigenetics

EZH2 is the catalytic subunit of Polycomb repressive complex 2 (PRC2), which is a highly conserved histone methyltransferase that targets lysine-27 of histone H3. This methylated H3-K27 chromatin mark is commonly associated with silencing of differentiation genes in organisms ranging from plants to flies to humans. Studies on human tumors show that EZH2 is frequently over-expressed in a wide variety of cancerous tissue types, including prostate and breast. Although the mechanistic contributions of EZH2 to cancer progression are not yet determined, functional links between EZH2-mediated histone methylation and DNA methylation suggest partnership with the gene silencing machinery implicated in tumor suppressor loss. Here we review the basic molecular biology of EZH2 and the findings that implicate EZH2 in different cancers. We also discuss EZH2 connections to other silencing enzymes, such as DNA methyltransferases and histone deacetylases, and we consider progress on deciphering mechanistic consequences of EZH2 overabundance and its potential roles in tumorigenesis. Finally, we review recent findings that link EZH2 roles in stem cells and cancer, and we consider prospects for integrating EZH2 blockade into strategies for developing epigenetic therapies.     

Pairing phosphoinositides with calcium ions in endolysosomal dynamics: phosphoinositides control the direction and specificity of membrane trafficking by regulating the activity of calcium channels in the endolysosomes

The direction and specificity of endolysosomal membrane trafficking is tightly regulated by various cytosolic and membrane-bound factors, including soluble NSF attachment protein receptors (SNAREs), Rab GTPases, and phosphoinositides. Another trafficking regulatory factor is juxta-organellar Ca(2+) , which is hypothesized to be released from the lumen of endolysosomes and to be present at higher concentrations near fusion/fission sites. The recent identification and characterization of several Ca(2+) channel proteins from endolysosomal membranes has provided a unique opportunity to examine the roles of Ca(2+) and Ca(2+) channels in the membrane trafficking of endolysosomes. SNAREs, Rab GTPases, and phosphoinositides have been reported to regulate plasma membrane ion channels, thereby suggesting that these trafficking regulators may also modulate endolysosomal dynamics by controlling Ca(2+) flux across endolysosomal membranes. In this paper, we discuss the roles of phosphoinositides, Ca(2+) , and potential interactions between endolysosomal Ca(2+) channels and phosphoinositides in endolysosomal dynamics.     

Multiple roles of calcium ions in the regulation of neurotransmitter release

The intracellular calcium concentration ([Ca(2+)]) has important roles in the triggering of neurotransmitter release and the regulation of short-term plasticity (STP). Transmitter release is initiated by quite high concentrations within microdomains, while short-term facilitation is strongly influenced by the global buildup of "residual calcium." A global rise in [Ca(2+)] also accelerates the recruitment of release-ready vesicles, thereby controlling the degree of short-term depression (STD) during sustained activity, as well as the recovery of the vesicle pool in periods of rest. We survey data that lead us to propose two distinct roles of [Ca(2+)] in vesicle recruitment: one accelerating "molecular priming" (vesicle docking and the buildup of a release machinery), the other promoting the tight coupling between releasable vesicles and Ca(2+) channels. Such coupling is essential for rendering vesicles sensitive to short [Ca(2+)] transients, generated during action potentials.     

FBF-1 and FBF-2 regulate the size of the mitotic region in the C. elegans germline

In the C. elegans germline, GLP-1/Notch signaling and two nearly identical RNA binding proteins, FBF-1 and FBF-2, promote proliferation. Here, we show that the fbf-1 and fbf-2 genes are largely redundant for promoting mitosis but that they have opposite roles in fine-tuning the size of the mitotic region. The mitotic region is smaller than normal in fbf-1 mutants but larger than normal in fbf-2 mutants. Consistent with gene-specific roles, fbf-2 expression is limited to the distal germline, while fbf-1 expression is broader. The fbf-2 gene, but apparently not fbf-1, is controlled by GLP-1/Notch signaling, and the abundance of FBF-1 and FBF-2 proteins is limited by reciprocal 3'UTR repression. We propose that the divergent fbf genes and their regulatory subnetwork enable a precise control over size of the mitotic region. Therefore, fbf-1 and fbf-2 provide a paradigm for how recently duplicated genes can diverge to fine-tune patterning during animal development.     

拟南芥短肽激素PROPEP基因家族在根生长中的作用机理

AtPROPEP是拟南芥(Arabidopsis thaliana)具有7个成员的基因家族, 编码内源短肽激素。AtPROPEP基因家族编码的蛋白质C端23个氨基酸短肽能够被2个同源激酶受体AtPEPR1和AtPEPR2识别并结合, 引起下游反应。然而, 对于该家族成员AtPROPEP2,3−6的表达对茉莉酸(JA)和水杨酸(SA)的响应以及在根生长中的作用并不清楚。GUS染色和定量RT-PCR分析结果表明, AtPROPEP2–6的表达对于JA和SA的响应不同, 暗示着它们可能通过不同的方式参与植物的先天免疫反应。AtPROPEP3和AtPROPEP4过表达植株的表型分析表明, AtPROPEP3和AtPROPEP4促进拟南芥根的生长。     

Expression of the Argonaute protein PiwiL2 and piRNAs in adult mouse mesenchymal stem cells

Piwi (P-element-induced wimpy testis) first discovered in Drosophila is a member of the Argonaute family of micro-RNA binding proteins with essential roles in germ-cell development. The murine homologue of PiwiL2, also known as Mili is selectively expressed in the testes, and mice bearing targeted mutations of the PiwiL2 gene are male-sterile. PiwiL2 proteins are thought to protect the germ line genome by suppressing retrotransposons, stabilizing heterochromatin structure, and regulating target genes during meiosis and mitosis. Here, we report that PiwiL2 and associated piRNAs (piRs) may play similar roles in adult mouse mesenchymal stem cells. We found that PiwiL2 is expressed in the cytoplasm of metaphase mesenchymal stem cells from the bone marrow of adult and aged mice. Knockdown of PiwiL2 with a specific siRNA enhanced cell proliferation, significantly increased the number of cells in G1/S and G2/M cell cycle phases and was associated with increased expression of cell cycle genes CCND1, CDK8, microtubule regulation genes, and decreased expression of tumor suppressors Cables 1, LATS, and Cxxc4. The results suggest broader roles for Piwi in genome surveillance beyond the germ line and a possible role in regulating the cell cycle of mesenchymal stem cells.     

Dermatan sulfate epimerase 2 is the predominant isozyme in the formation of the chondroitin sulfate/dermatan sulfate hybrid structure in postnatal developing mouse brain

Chondroitin sulfate (CS) and dermatan sulfate (DS) are expressed in significant amounts in the brain and play important roles in the development of the central nervous system in mammals. CS and DS structures are often found in a single CS/DS hybrid chain. The l-iduronic acid (IdoA)-containing domain, which defines a DS-type domain, appears key to the biological functions of the CS/DS hybrid chain. In this study, to clarify the distribution of the DS-type structure in the brain during development, the expression patterns of DS epimerase 1 (DS-epi1) and DS-epi2, both of which convert d-glucuronic acid into IdoA, were investigated by in situ hybridization. DS-epi2 was ubiquitously expressed in the developing brain after birth, whereas the expression of DS-epi1 was faint and obscure at all developmental stages. Quantitative real-time polymerase chain reaction revealed the expression of DS-epi2 to be higher than that of DS-epi1 throughout development, suggesting that DS-epi2 but not DS-epi1 is mostly expressed in the brain and plays key roles in the epimerization of CS/DS during its biosynthesis. Moreover, an analysis of the disaccharides of CS/DS demonstrated significant amounts of IdoA-containing iD units [IdoA(2S)-GalNAc(6S)] and iB units [IdoA(2S)-GalNAc(4S)], where 2S, 4S and 6S stand for 2-O-, 4-O- and 6-O-sulfate, respectively, in every region of the brain examined. The proportion of these units in cerebellar CS/DS was greatly altered during postnatal development. These results suggest that the IdoA-containing structures in the developing brain are mainly produced by the actions of DS-epi2 and play crucial roles in postnatal development.