Where, when and how much: regulation of myelin proteolipid protein gene expression

The myelin proteolipid protein (PLP) gene (Plp) encodes the most abundant protein found in myelin from the central nervous system (CNS). Expression of the gene is regulated in a spatiotemporal manner with maximal levels of expression occurring in oligodendrocytes during the active myelination period of CNS development, although other cell types in the CNS as well as in the periphery can express the gene to a much lower degree. In oligodendrocytes, Plp gene expression is tightly regulated. Underexpression or overexpression of the gene has been shown to have adverse effects in humans and other vertebrates. In light of this strict control, this review provides an overview of the current knowledge of Plp gene regulation.Received 4 August 2003; received after revision 17 September 2003; accepted 24 September 2003     

Melatonin regulation of antioxidant enzyme gene expression

Antioxidant enzymes (AOEs) are part of the primary cellular defense against free radicals induced by toxins and/or spontaneously formed in cells. Melatonin (MLT) has received much attention in recent years due to its direct free radical scavenging and antioxidant properties. In the present work we report that MLT, at physiological serum concentrations (≈ 1 nM), increases the mRNA of both superoxide dismutases (SODs) and glutathione peroxidase (GPx) in two neuronal cell lines. The MLT effect on both SODs and GPx mRNA was mediated by a de novo synthesized protein. MLT alters mRNA stability for Cu-Zn SOD and GPx. Experiments with a short time treatment (pulse action) of MLT suggest that the regulation of AOE gene expression is likely to be receptor mediated, because 1-h treatment with MLT results in the same response as a 24-h treatment. Received 18 June 2002; received after revision 5 August 2002; accepted 27 August 2002 RID="*" ID="*"Corresponding author.     

Issues surrounding sleep-dependent memory consolidation and plasticity

There is a growing body of evidence in support of sleep-dependent memory consolidation and plasticity. However, there are also examples of memory development and plasticity in the absence of sleep, casting doubt on an exclusive sleep-dependent memory hypothesis. As a result, polarized stances have arisen within the field. Here we reflect on these findings, and explore how they maybe reconcilable in a unified approach to understanding the roles of wake, sleep and specific sleep stages in successful memory processing and brain plasticity.Received 6 August 2004; received after revision 28 September 2004; accepted 5 October 2004     

Molecular biology of chloroplast biogenesis: gene expression, protein import and intraorganellar sorting

The chloroplast is the hallmark organelle of plants. It performs photosynthesis and is therefore required for photoautotrophic plant growth. The chloroplast is the most prominent member of a family of related organelles termed plastids which are ubiquitous in plant cells. Biogenesis of the chloroplast from undifferentiated proplastids is induced by light. The generally accepted endosymbiont hypothesis states that chloroplasts have arisen from an internalized cyanobacterial ancestor. Although chloroplasts have maintained remnants of the ancestral genome (plastome), the vast majority of the genes encoding chloroplast proteins have been transferred to the nucleus. This poses two major challenges to the plant cell during chloroplast biogenesis: First, light and developmental signals must be interpreted to coordinately express genetic information contained in two distinct compartments. This is to ensure supply and stoichiometry of abundant chloroplast components. Second, developing chloroplasts must efficiently import nuclear encoded and cytosolically synthesized proteins. A subset of proteins, including such encoded by the plastome, must further be sorted to the thylakoid compartments for assembly into the photosynthetic apparatus. Received 1 September 2000; received after revision 27 October 2000; accepted 1 November 2000     

Heat shock protein gene expression during Xenopus development

Stress-induced heat shock protein gene expression is developmentally regulated during early embryogen esis of the frog, Xenopus laevis. For example, a number of heat shock protein genes, such as hsp70, hsp90, and ubiquitin are not heat-inducible until after the midblastula stage of embryogenesis. Furthermore, the family of small heat shock protein genes, hsp30, are differentially expressed after the midblastula stage as well as being regulated at the level of mRNA stability. Many of these stress proteins are also synthesized constitutively during oogenesis and embryogenesis during which they may act as molecular chaperones as well as being involved in sequestering proteins in an inactive state until required by the developing embryo. Furthermore the induction of these stress protein genes has been correlated with enhanced thermoresistance. During stressful conditions heat shock proteins probably prevent aggregation or misfolding of damaged protei ns within the embryo.     

Neurodegeneration changes in primary central nervous system neurons transfected with the Alzheimer-associated neuronal thread protein gene

The AD7c-NTP gene is over-expressed in brains with Alzheimer's disease (AD), and increased levels of the corresponding protein are detectable in cortical neurons, brain tissue extracts, cerebrospinal fluid, and urine beginning early in the course of AD neurodegeneration. In the present study, we utilized a novel method to transfect post-mitotic primary neuronal cell cultures, and demonstrated that over-expression of the AD7c-NTP gene causes cell death and neuritic sprouting, two prominent abnormalities associated with AD. These results provide further evidence that aberrantly increas-ed AD7c-NTP expression may have a role in AD-type neurodegeneration. In addition, we demonstrate that primary post-mitotic neurons can be efficiently transfected with conventional recombinant plasmid DNA to evaluate the effects of gene over-expression in relevant in vitro models. Received 31 January 2001; received after revision 31 March 2001; accepted 4 April 2001     

Recombinant expression of perchloric acid-soluble protein reduces cell proliferation

Perchloric acid-soluble protein (PSP) may play an important role in the regulation of cellular physiological functions because it has been highly conserved throughout evolution; however, this role has not been well elucidated. In previous reports, we suggested that PSP regulates cell proliferation. In this study, we examined the effect of PSP expression on proliferation of the normal rat kidney cell line NRK-52E, the rat hepatocyte cell line RLN-10, and the rat hepatoma cell line dRLh-84. Cells transfected with pcDNA-sense-PSP (pcDNA-S-PSP) over-expressed PSP mRNA and protein, and cell proliferation of the transfected cells was suppressed compared with that of cells transfected with pcDNA-empty (pcDNA-E). Cell viability of pcDNA-S-PSP-transfected cells was similar to that of pcDNA-E-transfected cells. Thus, over-expression of PSP suppresses cell proliferation without any influence on cell viability. These findings are the first to report an inhibitory activity of PSP on cell proliferation. Received 27 April 2001; received after revision 8 June 2001; accepted 8 June 2001     

疼痛的神经生物学--理解大脑机制及神经疾病治疗的机理

中枢神经系统的神经元和突触具有可塑性,他们能够发生贯穿整个生命过程的长时程改变。研究这种长时程变化的分子和细胞学机制,不仅可以帮助我们了解大脑如何学习和储存新的知识,而且还可以揭示机体损伤后病理变化的机制。我认为,一方面学习和记忆等生理学功能的神经机制可能与大脑在疼痛期间的反常或机体损伤相关的变化过程共用一些信号分子;另一方面,一些不参与认知学习和记忆过程的突触和神经元网络机制也可能与疼痛的病理过程相关。伤害性感受可以从脊髓传递到前脑并在不同水平受到调节。其中,前扣带脑皮质(anterior cingulate cortex,ACC)在痛觉的感受和调节中具有重要作用。我们的实验结果表明,ACC中的N-甲基-D-门冬氨酸(NMDA)受体依赖的、钙／钙调蛋白激活的腺苷酸环化酶(adenylyl cyclases,AC)(ACl和ACB)在慢性痛的表达过程中起着重要的作用。ACC还可以通过激活内源性易化系统影响脊髓背角的痛觉信号传递。这些结果为机体对损伤的生理反应如痛行为反应、情绪变化和不良记忆等提供了重要的突触和分子水平的机制。加强对疼痛机制研究,会带动中国的神经科学的基础和临床研究。     

If phosphatases go up, memory goes down

Previous work has provided conclusive support for a role of various protein kinases in processes underlying learning and memory formation. While these processes are not yet established in full detail, it is interesting to entertain the idea of protein phosphatases being involved in such mechanisms as well. Recent advances in this respect have provided preliminary support of this view. From the pharmacological as well as the transgenic analysis, it appears that especially the calcineurin/inhibitor-1 cascade plays an important role in the transition of intermediate-term into long-term memory formation.     

Conserved eukaryotic transposable elements and the evolution of gene regulation

Multiple remnants of transposable elements preserved in cis-regulatory modules may represent a record of mutations that were critical to the evolution of gene regulation and speciation. Received 13 August 2007; received after revision 8 October 2007; accepted 23 October 2007     

Sensing life: regulation of sensory neuron survival by neurotrophins

Neurotrophins are a family of structurally and functionally related neurotrophic factors which, in mammals, include: nerve growth factor, brain-derived neurotrophic factor, neurotrophin-3 (NT-3), and NT-4/5. In addition to their canonical role in promoting neuronal survival, these molecules appear to regulate multiple aspects of the development of the nervous system in vertebrates, including neuronal differentiation, axon elongation and target innervation, among others. Actions of neurotrophins and of their receptors in vivo are being analyzed by loss-of-function or gain-of-function experiments in mice. Here, we review the phenotypes of the primary sensory system in these mutant mouse strains and the different strategies specifically involved in the regulation of neuronal survival by neurotrophins in this portion of the nervous system. Received 10 December 2001; received after revision 11 May 2002; accepted 13 May 2002 RID="*" ID="*"Corresponding author.     

Altered proteoglycan gene expression and the tumor stroma

Tumor stroma is a specialized form of tissue that is associated with epithelial neoplasms. Recent evidence indicates that significant changes in proteoglycan content occur in the tumor stroma and that these alterations could support tumor progression and invasion as well as tumor growth. Our main hypothesis is that the generation of tumor stroma is under direct control of the neoplastic cells and that, via a feedback loop, altered proteoglycan gene expression would influence the behavior of tumor cells. In this review, we will focus primarily on the work from our laboratory related to the altered expression of chondroitin sulfate proteoglycan and its role in tumor development and progression. The connective tissue stroma of human colon cancer is enriched in chondroitin sulfate and the stromal cell elements, primarily colon fibroblasts and smooth muscle cells, are responsible for this biosynthetic increase. These changes can be reproduced in vitro by using either tumor metabolites or co-cultures of human colon carcinoma cells and colon mesenchymal cells. The levels of decorin, a leucine-rich proteoglycan involved in the regulation of matrix assembly and cell proliferation, are markedly elevated in the stroma of colon carcinoma. These changes correlate with a marked increase in decorin mRNA levels and a concurrent hypomethylation of decorin gene, a DNA alteration associated with enhanced gene expression. Elucidation of decorin gene structure has revealed an unexpected degree of complexity in the 5 untranslated region of the gene with two leader exons that are alternatively spliced to the second coding exon. Furthermore, a transforming growth factor beta (TGF-)-negative element is present in the promoter region of decorin gene. This regulatory domain is likely to be implicated in the silencing of decorin gene by TGF- and may contribute to the regulation of this matrix gene in the tumor stroma.