Cell cycle-dependent gene networks for cell proliferation activated by nuclear CK2α complexes.

Nuclear expression of protein kinase CK2α is reportedly elevated in human carcinomas, but mechanisms underlying its variable localization in cells are poorly understood. This study demonstrates a functional connection between nuclear CK2 and gene expression in relation to cell proliferation. Growth stimulation of quiescent human normal fibroblasts and phospho-proteomic analysis identified a pool of CK2α that is highly phosphorylated at serine 7. Phosphorylated CK2α translocates into the nucleus, and this phosphorylation appears essential for nuclear localization and catalytic activity. Protein signatures associated with nuclear CK2 complexes reveal enrichment of apparently unique transcription factors and chromatin remodelers during progression through the G1 phase of the cell cycle. Chromatin immunoprecipitation-sequencing profiling demonstrated recruitment of CK2α to active gene loci, more abundantly in late G1 phase than in early G1, notably at transcriptional start sites of core histone genes, growth stimulus-associated genes, and ribosomal RNAs. Our findings reveal that nuclear CK2α complexes may be essential to facilitate progression of the cell cycle, by activating histone genes and triggering ribosomal biogenesis, specified in association with nuclear and nucleolar transcriptional regulators.

Rosmarinic acid suppresses tau phosphorylation and cognitive decline by downregulating the JNK signaling pathway.

Rosmarinic acid (RA), a polyphenol found in Lamiaceae herbs, is a candidate of preventive ingredients against Alzheimer's disease (AD) as it potently suppresses the aggregation of amyloid ß (Aß); however, the effect of RA on tau phosphorylation and cognitive dysfunction remains unclear. The present study revealed that RA intake inhibited the pathological hallmarks of AD, including Aß and phosphorylated tau accumulation, and improved cognitive function in the 3 × Tg-AD mouse model. Additionally, RA intake suppressed hippocampal inflammation and led to the downregulation of the JNK signaling pathway that induces tau phosphorylation. Feeding with RA exerted an anti-inflammatory effect not only in the central nervous system but also in the periphery. Downregulation of the JNK signaling pathway in hippocampus may be a potential mechanism underlying the inhibition of progression of pathology and cognitive deficit by RA feeding.

Effects of Kudoa septempunctata infections in a human intestinal epithelial model (Caco-2): a DNA microarray study.

Kudoa septempunctata, a myxosporean parasite infecting the trunk muscles of olive flounder (Paralichthys olivaceus), is reported to cause food poisoning in humans. The molecular mechanisms underlying the toxicity of K. septempunctata spores remain largely unknown. In the present study, we examine the molecular basis of such toxicity using DNA microarray analysis of K. septempunctata-inoculated human colon adenocarcinoma cells (Caco-2). We observed that the transepithelial resistance of the K. septempunctata-inoculated Caco-2 cell monolayers decreased markedly. DNA microarray analysis revealed that the mRNA expression profiles of control and inoculated cells clearly differed. Inflammatory and bacteria-related pathways, such as interleukin-8 (IL-8) production and MAPK/NF-kappa B pathway, were enriched. The concentrations of IL-8 and serotonin (5-HT) were higher in inoculated cells than in controls. K. septempunctata invasion damages the human intestinal epithelium, causing increased production of IL-8 and 5-HT, which likely results in the vomiting associated with K. septempunctata invasion.Abbreviations: AP-1: activator protein 1; DAVID: Database for Annotation, Visualization and Integrated Discovery; ENS: enteric nervous system; FARMS: Factor Analysis for Robust Microarray Summarization; FDR: false discovery rate; GO: Gene Ontology; 5-HT: 5-hydroxytryptamine; IL-8: Interleukin-8; KEGG: Kyoto Encyclopedia of Genes and Genomes; K. septempunctata: Kudoa septempunctata; NF-kappa B: nuclear factor-kappa B; TJ: tight junction; TER: transepithelial electrical resistance.

Rosmarinic acid suppresses Alzheimer's disease development by reducing amyloid ß aggregation by increasing monoamine secretion.

A new mechanism is revealed by which a polyphenol, rosmarinic acid (RA), suppresses amyloid ß (Aß) accumulation in mice. Here we examined the brains of mice (Alzheimer's disease model) using DNA microarray analysis and revealed that the dopamine (DA)-signaling pathway was enhanced in the group fed RA versus controls. In the cerebral cortex, the levels of monoamines, such as norepinephrine, 3,4-dihydroxyphenylacetic acid, DA, and levodopa, increased after RA feeding. The expression of DA-degrading enzymes, such as monoamine oxidase B (Maob), was significantly downregulated in the substantia nigra and ventral tegmental area, both DA synthesis regions. Following in vitro studies showing that monoamines inhibited Aß aggregation, this in vivo study, in which RA intake increased concentration of monoamine by reducing Maob gene expression, builds on that knowledge by demonstrating that monoamines suppress Aß aggregation. In conclusion, RA-initiated monoamine increase in the brain may beneficially act against AD.

Redox Cycling Realized in Paper-Based Biochemical Sensor for Selective Detection of Reversible Redox Molecules Without Micro/Nano Fabrication Process.

This paper describes a paper-based biochemical sensor that realizes redox cycling with close interelectrode distance. Two electrodes, the generator and collector electrodes, can detect steady-state oxidation and reduction currents when suitable potential is held at each electrode. The sensor has two gold plates on both sides of a piece of chromatography paper and defines the interelectrode distance by the thickness of the paper (180 µm) without any micro-fabrication processes. Our proposed sensor geometry has successfully exhibited signatures of redox cycling. As a result, the concentration of ferrocyanide as reversible redox molecules was successfully quantified under the interference by ascorbic acid as a strong irreversible reducing agent. This was possible because the ascorbic acids are completely consumed by the irreversible reaction, while maintaining redox cycling of reversible ferrocyanide. This suggests that a sensor based on the redox cycling method will be suitable for detecting target molecules at low concentration.