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Pathways Underlying (pathway + underlying)
Selected AbstractsActivation of p53 signalling in acetylsalicylic acid-induced apoptosis in OC2 human oral cancer cellsEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 10 2003C.-C. Ho Abstract Background, Nonsteroidal anti-inflammatory drugs (NSAIDs) such as acetylsalicylic acid (ASA, aspirin) are well known chemotherapeutic agents of cancers; however, the signalling molecules involved remain unclear. The aim of this study was to investigate the possible existence of a putative p53-dependent pathway underlying the ASA-induced apoptosis in OC2 cells, a human oral cancer cell line. Materials and methods, The methyl tetrazolium (MTT) assay was employed to quantify differences in cell viability. DNA ladder formation on agarose electrophoresis was used as apoptosis assay. The expression levels of several master regulatory molecules controlling various signal pathways were monitored using the immunoblotting techniques. Flow cytometry was used to confirm the effect of ASA on cell cycle. Patterns of changes in expression were scanned and analyzed using the NIH image 1·56 software (NIH, Bethesda, MD, USA). All the data were analyzed by anova. Results, Acetylsalicylic acid reduced cell viability and presence of internucleosomal DNA fragmentation. In the meanwhile, phosphorylation of p53 at serine 15, accumulation of p53 and increased the expression of its downstream target genes, p21 and Bax induced by ASA. The expression of cyclooxygenase-2 was suppressed. Disruption of p53-murine double minute-2 (MDM2) complex formation resulted in increasing the expression of MDM2 60-kDa cleavage fragment. Inhibited the activation of p42/p44 mitogen-activated protein kinase (MAPK) by PD98059, a specific inhibitor of extracellular regulatory kinase (ERK), significantly decreased cell viability and enhanced the expression of p53 induced by ASA. The result of the cell-cycle analysis showed that ASA and PD98059 induced the cell cycle arrested at the G0/G1 phase and resulted in apoptosis. Conclusion, Nonsteroidal anti-inflammatory drug-inhibited cyclooxygenase is not the only or even the most important mechanism of inhibition. Our study presents evidences that activation of p53 signalling involved in apoptosis induced by ASA. Furthermore, the apoptotic effect was enhanced by blocking the activation of p42/p44 MAPK in response to treatment with ASA, thus indicating a negative role for p42/p44 MAPK. [source] Mechanisms of metabotropic glutamate receptor-mediated synaptic signalling in cerebellar Purkinje cellsACTA PHYSIOLOGICA, Issue 1 2009J. Hartmann Abstract The metabotropic glutamate receptors type 1 (mGluR1s) are required for a normal function of the mammalian cerebellum. These G-protein-coupled receptors are abundantly expressed in the principle cerebellar cells, namely the Purkinje neurones. Under physiological conditions, mGluR1s are activated during repetitive activity of both afferent glutamatergic synaptic inputs provided by the climbing and parallel fibres respectively. Unlike the common ionotropic glutamate receptors that underlie rapid synaptic excitation, mGluR1s produce a complex post-synaptic response consisting of a Ca2+ -release signal from intracellular stores and a slow excitatory post-synaptic potential. While it is well established that the mGluR1-dependent Ca2+ -release signal from intracellular stores involves the activation of inositol-trisphosphate receptors, the mechanisms underlying the slow synaptic excitation remained unclear. Here we will review recent evidence indicating an essential role of C-type transient receptor potential (TRPC) cation channels, especially that of the subunit TRPC3, for the generation of the mGluR1-dependent synaptic current. For the signalling pathways underlying both, Ca2+ -release from intracellular stores and the slow synaptic potential, we present current knowledge about the activators, downstream effectors and possible roles for mGluR1-dependent signalling in Purkinje neurones. [source] Hippocampal lesions impair spatial memory performance, but not song,A developmental study of independent memory systems in the zebra finchDEVELOPMENTAL NEUROBIOLOGY, Issue 8 2009David J. Bailey Abstract Songbirds demonstrate song- and spatial-learning, forms of memory that appear distinct in formal characteristics and fitting the descriptions and criteria of procedural and episodic-like memory function, respectively. As in other vertebrates, the neural pathways underlying these forms of memory may also be dissociable, and include the corresponding song circuit and hippocampus (HP). Whether (or not) these two memory systems interact is unknown. Interestingly, the HP distinguishes itself as a site of immediate early gene expression in response to song and as a site of estrogen synthesis, a steroid involved in song learning. Thus, an interaction between these memory systems and their anatomical substrates appears reasonable to hypothesize, particularly during development. To test this idea, juvenile male or female zebra finches received chemical lesions of the HP at various points during song learning, as did adults. Song structure, singing behavior, song preference, and spatial memory were tested in adulthood. Although lesions of the HP severely compromised HP-dependent spatial memory function across all ages and in both sexes, we were unable to detect any effects of HP lesions on song learning, singing, or song structure in males. Interestingly, females lesioned as adults, but not as juveniles, did lose the characteristic preference for their father's song. Since compromise of the neural circuits that subserve episodic-like memory does very little (if anything) to affect procedural-like (song learning) memory, we conclude that these memory systems and their anatomical substrates are well dissociated in the developing male zebra finch. © 2009 Wiley Periodicals, Inc. Develop Neurobiol 2009 [source] Different signaling pathways in the livers of patients with chronic hepatitis B or chronic hepatitis C,HEPATOLOGY, Issue 5 2006Masao Honda The clinical manifestations of chronic hepatitis B (CH-B) and chronic hepatitis C (CH-C) are different. We previously reported differences in the gene expression profiles of liver tissue infected with CH-B or CH-C; however, the signaling pathways underlying each condition have yet to be clarified. Using a newly constructed cDNA microarray consisting of 9614 clones selected from 256,550 tags of hepatic serial analysis of gene expression (SAGE) libraries, we compared the gene expression profiles of liver tissue from 24 CH-B patients with those of 23 CH-C patients. Laser capture microdissection was used to isolate hepatocytes from liver lobules and infiltrating lymphoid cells from the portal area, from 16 patients, for gene expression analysis. Furthermore, the comprehensive gene network was analyzed using SAGE libraries of CH-B and CH-C. Supervised and nonsupervised learning methods revealed that gene expression was correlated more with the infecting virus than any other clinical parameters such as histological stage and disease activity. Pro-apoptotic and DNA repair responses were predominant in CH-B with p53 and 14-3-3 interacting genes having an important role. In contrast, inflammatory and anti-apoptotic phenotypes were predominant in CH-C. These differences would evoke different oncogenic factors in CH-B and CH-C. In conclusion, we describe the different signaling pathways induced in the livers of patients with CH-B or CH-C. The results might be useful in guiding therapeutic strategies to prevent the development of hepatocellular carcinoma in cases of CH-B and CH-C. (HEPATOLOGY 2006;44:1122,1138.) [source] Effects of estrogen and androgen deprivation on the progression of non-alcoholic steatohepatitis (NASH) in male Sprague,Dawley ratsHEPATOLOGY RESEARCH, Issue 9 2009Yanjun Mu Aim:, We studied the mechanisms of estrogen/androgen involvement in the induction of NASH by treating Sprague,Dawley (SD) rats fed with a normal or high fat (HF) diet by depriving them of endogenous estrogens/androgens. Methods:, Male adult SD rats (n = 10/group) on normal or HF diets were treated for 75 days either with tamoxifen (Tam) or flutamide (Flu) or Tam + Flu in order to induce NASH. We analyzed histopathologically the liver samples from the treated groups for NASH, checked the serum biochemical and lipid profile markers and finally analyzed the signal pathways underlying the molecular mechanisms for the induction process of NASH. Results:, Deprivation of endogenous estrogens and/or androgens (Tam or Flu or Tam + Flu) without the HF diet did not induce NASH. Tam or Tam + Flu induced NASH, compared to milder lesions without fibrosis in HF diet and Flu-treated liver. Serum alanine aminotransferase or lipid profile markers further proved the Tam, Flu or Tam + Flu effects on the induction of NASH in conjunction with a HF diet. Tam treatment predominantly downregulated the ER, and FAS and upregulated UCP2 and TNF-,. Conclusions:, Deprivation of endogenous estrogen/androgens in conjunction with a HF diet may induce NASH where the downregulated ER, and FAS, and upregulated UCP2 and TNF-, could be involved in their molecular pathomechanism pathways. These results could suggest the potential negative roles of estrogenic/androgenic depriving compounds in the induction of NASH, along with obesity. [source] Stem Cell Review Series: Regulating highly potent stem cells in aging: environmental influences on plasticityAGING CELL, Issue 4 2008Jay M. Edelberg Summary Significant advances in the past decade have revealed that a large number of highly plastic stem cells are maintained in humans through adulthood and are present even in older adults. These findings are notable in light of the reduced capacity for repair and regeneration in older tissues. The apparent dichotomy can be reconciled through an appreciation of the age-associated changes in the microenvironmental pathways that govern adult stem cell plasticity and differentiation patterns. Specifically, the recent identification of the age-related loss of the local platelet-derived growth factor signals that promote the induction of cardiac myocytes from Oct-3/4+ bone marrow stem cells, rather than impairment in the stem cells themselves, provides a template for understanding and targeting the environmental pathways underlying the regenerative capacity of older tissues and organs. It is projected that this paradigm extends to the overall regulation of adult stem cell biology, shifting the balance from tissue generation during development and maturation to the prevention of untoward stem cell differentiation with aging. [source] Genome-wide linkage of obstructive sleep apnoea and high-density lipoprotein cholesterol in a Filipino family: bivariate linkage analysis of obstructive sleep apnoeaJOURNAL OF SLEEP RESEARCH, Issue 2 2010BRONWYN L. RELF Summary Increasing evidence supports an association between obstructive sleep apnoea (OSA) and metabolic syndrome (MeS) in both children and adults, suggesting a genetic component. However, the genetic relationship between the diseases remains unclear. We performed a bivariate linkage scan on a single Filipino family with a high prevalence of OSA and MeS to explore the genetic pathways underlying these diseases. A large rural family (n = 50, 50% adults) underwent a 10-cM genome-wide scan. Fasting blood was used to measure insulin, triglycerides, total cholesterol and high density lipoprotein (HDL) cholesterol. Attended overnight polysomnography was used to quantify the respiratory disturbance index (RDI), a measure of sleep apnoea. Body mass index z -scores and insulin resistance scores were calculated. Bivariate multipoint linkage analyses were performed on RDI and MeS components. OSA prevalence was 46% (n = 23; nine adults, 14 children) in our participants. MeS phenotype was present in 40% of adults (n = 10) and 48% of children (n = 12). Linkage peaks with a logarithm of odds (LOD) score >3 were demonstrated on chromosome 19q13.4 (LOD = 3.04) for the trait pair RDI and HDL cholesterol. Candidate genes identified in this region include the killer cell immunoglobulin-like receptor genes. These genes are associated with modulating inflammatory responses in reaction to cellular stress and initiation of atherosclerotic plaque formation. We have identified a novel locus for genetic links between RDI and lipid factors associated with MeS in a chromosomal region containing genes associated with inflammatory responses. [source] Studies of twins: what can they tell us about the fetal origins of adult disease?PAEDIATRIC & PERINATAL EPIDEMIOLOGY, Issue 2005Ruth Morley Summary There has been much interest in evidence that people with lower birthweight have higher risk of adult cardiovascular disease, but the causal pathways underlying such observations are uncertain. Study of twins offers an opportunity to shed light on the underlying causal pathways, in particular by investigating the role of ,shared' factors vs. factors affecting each individual fetus. This involves comparing results of within-cohort vs. within-pair analyses. Twins share many factors during gestation but birthweight discordance (difference in birthweight within a twin pair) cannot be determined by these shared factors and must relate to factors affecting growth of each individual fetus. If associations seen in a cohort of twins remain in within-pair analyses, then factors specific to each individual must be involved in the underlying causal pathways. Conversely, if the relationships disappear or substantially diminish in within-pair analyses, then factors common to the pair must be involved. Comparison of findings in monozygotic vs. dizygotic twins may provide insights into the role of genetic factors, although issues related to chorionicity need to be taken into account. We tabulate published data and conclude that differences in methodology and analyses preclude informative meta-analysis, and that analysis of pooled data would provide more useful information. [source] Seeing the anatomy of hearing: New tools and approaches chart the pathways underlying how we process and integrate soundTHE ANATOMICAL RECORD : ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY, Issue 4 2006Jeffrey T. Laitman Associate Editor, The Anatomical Record No abstract is available for this article. [source] Cancer stem cells: lessons from leukaemiaCELL PROLIFERATION, Issue 6 2005D. Bonnet Leukaemia can indeed be viewed as aberrant haematopoietic processes initiated by rare leukaemic stem cells that have maintained or reacquired the capacity for indefinite proliferation through accumulated mutations and/or epigenetic changes. Yet, despite their critical importance, much remains to be learned about the developmental origin of leukaemic stem cells and the molecular pathways underlying the transformation of normal cells into leukaemic stem cells. This report will review our current knowledge on leukaemic stem cells development and finally demonstrate how these discoveries provide a paradigm for identification of cancer stem cells from solid tumours. [source] | |||||||||||||