Redox Control of Signal Transduction,Gene Expression and Cellular Senescence

Reactive oxygen species (ROS) act as subcellular messengers in such complex cellular processes as mitogenic signal transduction, gene expression, regulation of cell proliferation, replicative senescence, and apoptosis. They serve to maintain cellular homeostasis and their production is under strict control. However, the mechanisms whereby ROS act are still obscure. Here we review recent advances in our understanding of signaling mechanisms and recent data about the involvement of ROS in: (i) the regulation of the mitogenic transduction elements, particularly protein kinases and phosphatases; (ii) the regulation of gene expression; and (iii) the induction of replicative senescence and the role, if any, in aging and age-related disorders.     

The nuclear localization signal and the C-terminal region of FHY1 are required for transmission of phytochrome A signals

Plants use the family of phytochrome photoreceptors to sense their light environment in the red/far-red region of the spectrum. Phytochrome A (phyA) is the primary photoreceptor that regulates germination and early seedling development. This phytochrome mediates seedling de-etiolation for the developmental transition from heterotrophic to photoauxotrophic growth. High intensity far-red light provides a way to specifically assess the role of phyA in this process and was used to isolate phyA-signaling intermediates. fhy1 and pat3 (renamed fhy1-3) are independently isolated alleles of a gene encoding a phyA signal transduction component. FHY1 is a small 24 kDa protein that shows no homology to known functional motifs, besides a small conserved septin-related domain at the C-terminus, a putative nuclear localization signal (NLS) and a putative nuclear exclusion signal (NES). Here we demonstrate that the septin-related domain is important for FHY1 to transmit phyA signals. Moreover, the putative NLS and NES of FHY1 are indeed involved in its nuclear localization and exclusion. Nuclear localization of FHY1 is needed for it to execute responses downstream of phyA. Together with the results from global expression analysis, our findings point to an important role of FHY1 in phyA signaling through its nuclear translocation and induction of gene expression.     

Hyperosmotic stress induces rapid synthesis of phosphatidyl-D-inositol 3,5-bisphosphate in plant cells

Cells from several different plant species synthesised a polyphosphoinositide (PPI)-like lipid when osmo-stressed. Synthesis was maximal after about 10 min and was stimulated by a variety of osmolytes. Using NaCl, the strongest response centred around 200 mM. The lipid was shown to be the novel PPI isomer phosphatidyl-inositol 3,5-bisphosphate [PtdIns-(3,5)P₂] by analytical thin-layer chromatography and conversion to PtdIns(3,4,5)P₃ using recombinant phosphoinositide 4-OH kinase. The results indicate that PtdIns-(3,5)P₂ plays a role in a general osmo-signalling pathway in plants. Its potential role is discussed. Received: 6 November 1998 / Accepted: 14 December 1998     

Gene delivery to airway epithelial cells in vivo: a direct comparison of apical and basolateral transduction strategies using pseudotyped lentivirus vectors

Lentivirus vectors are being investigated as gene delivery vehicles for cystic fibrosis airway gene therapy. Vesicular stomatitis virus G glycoprotein (VSV-G)-pseudotyped vectors transduce airway epithelia via receptors that are located predominantly on the basolateral surface of the airway epithelium. Effective transduction with VSV-G-pseudotyped vectors requires the use of a pre-treatment that disrupts epithelial tight junctions, allowing access to these basolateral receptors. In contrast, it has been reported that apically targeted lentiviral vectors allow efficient gene transfer in the absence of any pre-treatment. In a direct comparison of transduction by a VSV-G-pseudotyped vector, in combination with a pre-treatment with lysophosphatidylcholine (LPC), and the same vector pseudotyped with the apically targeted baculovirus GP64 envelope (without any pre-treatment), the GP64 vector was found to be significantly less efficient. However, when a pre-treatment with LPC was used the level of transduction with the GP64-pseudotyped lentiviral vector was not significantly different to that resulting from the VSV-G-pseudotyped vector. The cell types transduced with each vector were essentially the same, with the majority of cells transduced being respiratory (ciliated cells). However, unlike the VSV-G-pseudotyped vector, which results in persisting gene expression, transduction with the GP64-pseudotyped vector resulted in gene expression that declined to undetectable levels over six months, whether or not an LPC pre-treatment was used.     

Insulin signaling and glucose transport in insulin resistant human skeletal muscle

Insulin increases glucose uptake and metabolism in skeletal muscle by signal transduction via protein phosphorylation cascades. Insulin action on signal transduction is impaired in skeletal muscle from Type 2 diabetic subjects, underscoring the contribution of molecular defects to the insulin resistant phenotype. This review summarizes recent work to identify downstream intermediates in the insulin signaling pathways governing glucose homeostasis, in an attempt to characterize the molecular mechanism accounting for skeletal muscle insulin resistance in Type 2 diabetes. Furthermore, the effects of pharmaceutical treatment of Type 2 diabetic patients on insulin signaling and glucose uptake are discussed. The identification and characterization of pathways governing insulin action on glucose metabolism will facilitate the development of strategies to improve insulin sensitivity in an effort to prevent and treat Type 2 diabetes mellitus.     

Inflammatory cytokines activate p38 MAPK to induce osteoprotegerin synthesis by MG-63 cells

Inflammatory bone diseases are characterized by the presence of pro-inflammatory cytokines that regulate bone turnover. Osteoprotegerin (OPG) is a soluble osteoblast-derived protein that influences bone resorption by inhibiting osteoclast differentiation and activation. In the present study, we demonstrate that interleukin-1beta and tumor necrosis factor alpha induce OPG mRNA production and OPG secretion by osteoblast-like MG-63 cells. Maximum induction of OPG secretion by either cytokine requires activation of the p38 mitogen activated protein kinase (MAPK) pathway but neither the p42/p44 (ERK) nor the c-Jun N-terminal MAPK pathways. Induction of OPG mRNA by either cytokine is also p38 MAPK dependent. Taken together, these data indicate that cytokine-induced OPG gene expression and protein secretion are differentially regulated by specific MAP kinase signal transduction pathways.     

Toll样受体(TLRs)的信号转导与免疫调节

Toll样受体(Toll-like receptors,TLRs)是进化中比较保守的一个受体家族,至少包括10个成员.TLRs能特异地识别病原相关的分子模式(PAMPs),不仅在激活天然免疫中发挥重要的作用,而且还调节获得性免疫,是连接天然免疫和获得性免疫的桥梁.近年来,TLRs信号转导的研究,特别是在负调控研究领域,进展非常迅速.对TLRs信号通路新进展以及TLRs在抗感染免疫中的作用进行了综述.     

拟南芥油菜素内酯信号转导研究进展

油菜素内酯（brassinosteroid）信号首先被膜上的受体BRI1／BAK1复合体感知,然后在一系列蛋白参与下传递到核内,进一步调控下游基因的表达。本文综述了拟南芥中油菜素内酯信号转导研究的进展,并对今后的研究方向进行了探讨。     

昆虫嗅觉相关蛋白的研究进展

嗅觉是昆虫产生行为的重要物质基础,阐明昆虫嗅觉机理有助于调控昆虫行为和进行害虫治理。近年来,许多与嗅觉相关的生物活性分子和相关基因的发现和克隆,对揭示嗅觉机理具有重要作用。作者针对近年来研究较多的气味结合蛋白、化学感受蛋白、气味受体、气味降解酶以及感觉神经元膜蛋白等,就其生化特性、表达部位、分子结构、生理功能等进行了综述。     

Switching roles: the functional plasticity of adult tissue stem cells

Adult organisms have to adapt to survive, and the same is true for their tissues. Rates and types of cell production must be rapidly and reversibly adjusted to meet tissue demands in response to both local and systemic challenges. Recent work reveals how stem cell (SC) populations meet these requirements by switching between functional states tuned to homoeostasis or regeneration. This plasticity extends to differentiating cells, which are capable of reverting to SCs after injury. The concept of the niche, the micro‐environment that sustains and regulates stem cells, is broadening, with a new appreciation of the role of physical factors and hormonal signals. Here, we review different functions of SCs, the cellular mechanisms that underlie them and the signals that bias the fate of SCs as they switch between roles.