Polyamine-dependent gene expression

The polyamines spermidine and spermine along with the diamine putrescine are involved in many cellular processes, including chromatin condensation, maintenance of DNA structure, RNA processing, translation and protein activation. The polyamines influence the formation of compacted chromatin and have a well-established role in DNA aggregation. Polyamines are used in the posttranslational modification of eukaryotic initiation factor 5A, which regulates the transport and processing of specific RNA. The polyamines also participate in a novel RNA-decoding mechanism, a translational frameshift, of at least two known genes, the TY1 transposon and mammalian antizyme. Polyamines are crucial for their own regulation and are involved in feedback mechanisms affecting both polyamine synthesis and catabolism. Recently, it has become apparent that the polyamines are able to influence the action of the protein kinase casein kinase 2. Here we address several roles of polyamines in gene expression.Received 27 November 2002; received after revision 9 January 2003; accepted 31 January 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.     

Epigenetic regulation of mmp-9 gene expression

Matrix metalloproteinase 9 (MMP-9) is one of the most studied enzymes in cancer. MMP-9 can cleave proteins of the extracellular matrix and a large number of receptors and growth factors. Accordingly, its expression must be tightly regulated to avoid excessive enzymatic activity, which is associated with disease progression. Although we know that epigenetic mechanisms play a central role in controlling mmp-9 gene expression, predicting how epigenetic drugs could be used to suppress mmp-9 gene expression is not trivial because epigenetic drugs also regulate the expression of key proteins that can tip the balance towards activation or suppression of MMP-9. Here, we review how our understanding of the biology and expression of MMP-9 could be exploited to augment clinical benefits, most notably in terms of the prevention and management of degenerative diseases and cancer.     

Differential display analysis of gene expression in invertebrates

Screening for differentially expressed genes is a straightforward approach to study the molecular basis for changes in gene expression. Differential display analysis has been used by investigators in diverse fields of research since it was developed. Differential display has also been the approach of choice to investigate changes in gene expression in response to various biological challenges in invertebrates. We review the application of differential display analysis of gene expression in invertebrates, and provide a specific example using this technique for novel gene discovery in the nematode Caenorhabditis elegans.     

Memory formation and the regulation of gene expression

On a cellular level, formation of memory is based on a selective change in synaptic efficacy that is both fast and, in case of important information, long-lasting. Rapidity of cellular changes is achieved by modifying preexisting synaptic molecules (receptors, ion channels), which instantaneously alters the efficacy of synaptic transmission. Endurance, that is the formation of long-term memory (LTM), is based on transient and perhaps also long-lasting changes in protein synthesis. A number of different methods exist to interfere with the synthesis of specific proteins or proteins in general. Other methods, in turn, help to identify proteins whose synthesis is changed following learning. These mostly molecular methods are briefly described in the present review. Their successful application in a variety of memory paradigms in invertebrates and vertebrates is illustrated. The data support the importance of selective changes in gene expression for LTM. Proteins newly synthesized during memory consolidation are likely to contribute to restructuring processes at the synapse, altering the efficiency of transmission beyond the scope of STM. Increased or, less often, decreased synthesis of proteins appears during specific time windows following learning. Recent evidence supports older data suggesting that two or even more waves of protein synthesis exist during the consolidation period. It is expected that the new molecular methods will help to identify and characterize molecules whose expression changes during LTM formation even in complex vertebrate learning paradigms.     

Globin gene expression in MSV-transformed fibroblasts.

The activation of globin gene expression on viral transformation of 3T3 cells was investigated. Globin mRNA was determined using a radioactive complementary DNA probe. No difference was found between 3T3 and transformed 3T3 cells. There does not therefore appear to be a random activation of extensive regions of the cellular genome.     

Genetical effects of radiation and chemicals

Zusammenfassung Die populären Auffassungen der durch Bestrahlung erzeugten genetischen Schädigungen irren gewöhnlich weit vom Ziele, und zwar in entgegengesetzten Richtungen. Oft hört man die Behauptung, dass bestrahlte Eltern die Gefahr laufen, Missgeburten oder sonstwie anormale Nachkommen zu haben. Noch öfter werden die genetischen Gefahren ionisierender Strahlen als unbeträchtlich und nicht beachtenswert hingestellt. In Wirklichkeit sind diese Gefahren sehr ernst zu nehmen. Sie betreffen aber nicht Individuen, sondern die menschliche Rasse als Ganzes. Über ihre Natur sind wir gut unterrichtet, über ihr Ausmass können wir uns gegenwärtig nur sehr ungenaue Vorstellungen machen. Genetisch unterschwellige Strahlungsdosen gibt es nicht; die gesetzlich festgesetzte Toleranzdosis muss daher einen Kompromiss darstellen zwischen gegenwärtigem Nutzen und zukünftigen Gefahren.     

Kinetic analysis,size profiling,and bioenergetic association of DNA released by selected cell lines in vitro

Although circulating DNA (cirDNA) analysis shows great promise as a screening tool for a wide range of pathologies, numerous stumbling blocks hinder the rapid translation of research to clinical practice. This is related directly to the inherent complexity of the in vivo setting, wherein the influence of complex systems of interconnected cellular responses and putative DNA sources creates a seemingly arbitrary representation of the quantitative and qualitative properties of the cirDNA in the blood of any individual. Therefore, to evaluate the potential of in vitro cell cultures to circumvent the difficulties encountered in in vivo investigations, the purpose of this work was to elucidate the characteristics of the DNA released [cell-free DNA (cfDNA)] by eight different cell lines. This revealed three different forms of cfDNA release patterns and the presence of nucleosomal fragments as well as actively released forms of DNA, which are not only consistently observed in every tested cell line, but also in plasma samples. Correlations between cfDNA release and cellular origin, growth rate, and cancer status were also investigated by screening and comparing bioenergetics flux parameters. These results show statistically significant correlations between cfDNA levels and glycolysis, while no correlations between cfDNA levels and oxidative phosphorylation were observed. Furthermore, several correlations between growth rate, cancer status, and dependency on aerobic glycolysis were observed. Cell cultures can, therefore, successfully serve as closed-circuit models to either replace or be used in conjunction with biofluid samples, which will enable sharper focus on specific cell types or DNA origins.     

Loss of redundant gene expression after polyploidization in plants

Summary Based on chromosomal location data of genes encoding 28 biochemical systems in allohexaploid wheat,Triticum aestivum L. (genomes AABBDD), it is concluded that the proportions of systems controlled by triplicate, duplicate, and single loci are 57%, 25%, and 18% respectively.