Biomedical subjects

Ozlen Konu

Publications and source records attributed to Ozlen Konu.

5 recordsLinked to original sources

PubMed2006

Alternatively spliced Robo2 isoforms in zebrafish and rat.

Robo2, a member of the robo gene family, functions as a repulsive axon guidance receptor as well as a regulator of cell migration and tissue morphogenesis in different taxa. In this study, a novel isoform of the zebrafish robo2 (robo2_tv2), which included an otherwise alternatively spliced exon (CAE), has been characterized. Robo2_tv2 is expressed differentially in most non-neuronal tissues of adult zebrafish whereas robo2_tv1 expression to a great extent is restricted to the brain and eye. In zebrafish, robo2_tv2 exhibits a very-low-level basal expression starting from 1 day post fertilization until the mid-larval stages, at which time its expression increases dramatically and could be detected throughout adulthood. Our findings demonstrate that the amino acid sequence coded by CAE of the robo2 gene is highly conserved between zebrafish and mammals, and also contains conserved motifs shared with robo1 and robo4 but not with robo3. Furthermore, we provide an account of differential transcription of the CAE homolog in various tissues of the adult rat. These results suggest that the alternatively spliced robo2 isoforms may exhibit tissue specificity.

Alternative Splicing↗

PubMed2004

Nicotine coregulates multiple pathways involved in protein modification/degradation in rat brain.

Previously, we used cDNA microarrays to demonstrate that the phosphatidylinositol and MAP kinase signaling pathways are regulated by nicotine in different rat brain regions. In the present report, we show that, after exposure to nicotine for 14 days, ubiquitin, ubiquitin-conjugating enzymes, 20S and 19S proteasomal subunits, and chaperonin-containing TCP-1 protein (CCT) complex members are upregulated in rat prefrontal cortex (PFC) while being downregulated in the medial basal hypothalamus (MBH). In particular, relative to saline controls, ubiquitins B and C were upregulated by 33% and 47% (P<0.01), respectively, in the PFC. The proteasome beta subunit 1 (PSMB1) and 26S ATPase 3 (PSMC3) genes were upregulated in the PFC by 95% and 119% (P<0.001), respectively. In addition to the protein degradation pathway of the ubiquitin-proteasome complexes, we observed in the PFC an increase in the expression of small, ubiquitin-related modifiers (SUMO) 1 and 2 by 80% and 33%, respectively (P<0.001), and in 3 of 6 CCT subunits by up to 150% (P<0.0001). To a lesser extent, a change in the opposite direction was obtained in the expression of the same gene families in the MBH. Quantitative real-time RT-PCR was used to validate the microarray results obtained with some representative genes involved in these pathways. Taken together, our results suggest that, in response to systemic nicotine administration, the ubiquitin-proteasome, SUMO, and chaperonin complexes provide an intricate control mechanism to maintain cellular homeostasis, possibly by regulating the composition and signaling of target neurons in a region-specific manner.

Animals↗

PubMed2004

Application of a customized pathway-focused microarray for gene expression profiling of cellular homeostasis upon exposure to nicotine in PC12 cells.

Maintenance of cellular homeostasis is integral to appropriate regulation of cellular signaling and cell growth and division. In this study, we report the development and quality assessment of a pathway-focused microarray comprising genes involved in cellular homeostasis. Since nicotine is known to have highly modulatory effects on the intracellular calcium homeostasis, we therefore tested the applicability of the homeostatic pathway-focused microarray on the gene expression in PC-12 cells treated with 1 mM nicotine for 48 h relative to the untreated control cells. We first provided a detailed description of the focused array with respect to its gene and pathway content and then assessed the array quality using a robust regression procedure that allows for the exclusion of unreliable measurements while decreasing the number of false positives. As a result, the mean correlation coefficient between duplicate measurements of the arrays used in this study (control vs. nicotine treatment, three samples each) has increased from 0.974+/-0.017 to 0.995+/-0.002. Furthermore, we found that nicotine affected various structural and signaling components of the AKT/PKB signaling pathway and protein synthesis and degradation processes in PC-12 cells. Since modulation of intracellular calcium concentrations ([Ca(2+)](i)) and phosphatidylinositol signaling are important in various biological processes such as neurotransmitter release and tissue pathogenesis including tumor formation, we expect that the homeostatic pathway-focused microarray potentially can be used for the identification of unique gene expression profiles in comparative studies of drugs of abuse and diverse environmental stimuli, such as starvation and oxidative stress.

Animals↗

PubMed2003

Nicotine, body weight and potential implications in the treatment of obesity.

Obesity is an epidemic problem in the U. S. and many other industrialized nations. Historically, the drugs used for the treatment of obesity generally targeted small molecule neurotransmitters. As research grows to decipher the underlying molecular mechanisms behind energy homeostasis, it is becoming evident that the modulating effects of neuropeptides also are critical in the regulation of appetite and metabolism. The search for drugs to modify these monoaminergic and peptidergic pathways may eventually prove successful in the treatment of obesity. While tobacco smoking has long been used as one strategy to maintain a lower body weight, especially in female smokers, its adverse associations with addiction and disease overshadow its potential use as an antiobesity agent. Potential pharmacological effects of nicotine could be better understood as the intricacies of the nicotinic acetylcholine receptor are revealed. The objective of this review is threefold: first is to provide an overview of the physiological effects of nicotine on body weight while focusing on the drugs that are available as antiobesity and smoking cessation agents. Second is to provide the present status of the nicotinic acetylcholine receptor as it relates to energy homeostasis and its potential as an effective treatment modality for obesity. Third is to present the current knowledge with respect to nicotine's effects on energy homeostatic and reward related pathways at the molecular level. A better understanding of the regulatory mechanisms underlying the pharmacological effects of nicotine on body weight will provide insights in identification of potential targets for the development of appropriate medicines in the treatment of obesity.

Animals↗

PubMed2002

Correlations between mRNA expression levels and GC contents of coding and untranslated regions of genes in rodents.

Gene expression is regulated by a highly coordinated network of events whose efficiency may constrain the level of expression. Among other factors, natural selection for increased translational efficiency and/or fidelity may shape nucleotide composition and, hence, codon usage during evolution. Previous studies have shown that highly expressed genes in Saccharomyces cerevisiae, Caenorhabditis elegans, and Drosophila melanogaster have relatively higher codon usage biases. However, in the case of mammals, results have been equivocal. In this study, we assessed the correlation between nucleotide composition and mRNA expression levels of rodent genes measured by cDNA microarray and serial analysis of gene expression (SAGE) techniques. We found that mRNA expression levels were correlated with the third nucleotide position GC (GC3) content for both Rattus norvegicus (r = 0.246, p = 0.01; N = 110) and Mus musculus (r = 0.21, p = 0.0026; N = 203) genes. However, no significant correlation was evident between mRNA expression level and GC contents of 5'- and 3'-untranslated regions (UTRs) for either species. This suggests that, in rodents, nucleotide composition of coding sequences and UTRs might evolve differentially when considered along an expression gradient. Accordingly, it is possible that higher GC levels may present the rodent genes with a selective advantage for translational efficiency. However, the increase in GC3 content seems to level off above an expressional threshold (e.g., >or=threefold the median expression for R. norvegicus), suggesting that conflicting demands posed by different aspects of transcriptional and translational machineries (e.g., efficiency versus fidelity) may set an upper limit for GC3.

Animals↗