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Several Biological Processes (several + biological_process)
Selected AbstractsmiR-29b and miR-125a regulate podoplanin and suppress invasion in glioblastomaGENES, CHROMOSOMES AND CANCER, Issue 11 2010Maria Angelica Cortez Glioblastoma is the most frequent and malignant brain tumor, characterized by an elevated capacity for cellular proliferation and invasion. Recently, it was demonstrated that podoplanin membrane sialo-glycoprotein encoded by PDPN gene is over-expressed and related to cellular invasion in astrocytic tumors; however the mechanisms of regulation are still unknown. MicroRNAs are noncoding RNAs that regulate gene expression and several biological processes and diseases, including cancer. Nevertheless, their roles in invasion, proliferation, and apoptosis of glioblastoma are not completely understood. In this study, we focused on miR-29b and miR-125a, which were predicted to regulate PDPN, and demonstrated that these microRNAs directly target the 3, untranslated region of PDPN and inhibit invasion, apoptosis, and proliferation of glioblastomas. Furthermore, we report that miR-29b and miR-125a are downregulated in glioblastomas and also in CD133-positive cells. Taken together, these results suggest that miR-29b and miR-125a represent potential therapeutic targets in glioblastoma. © 2010 Wiley-Liss, Inc. [source] Autophagy activation by rapamycin eliminates mouse Mallory-Denk bodies and blocks their proteasome inhibitor-mediated formation,HEPATOLOGY, Issue 6 2008Masaru Harada The proteasomal and lysosomal/autophagy pathways in the liver and other tissues are involved in several biological processes including the degradation of misfolded proteins. Exposure of hepatocyte cell lines to proteasome inhibitors (PIs) results in the formation of inclusions that resemble Mallory-Denk bodies (MDBs). Keratins are essential for MDB formation and keratin 8 (K8)-overexpressing transgenic mice are predisposed to MDB formation. We tested the hypothesis that PIs induce MDBs in vivo and that autophagy participates in MDB turnover. The effect of the PI bortezomib (which is used to treat some malignancies) on MDB formation was tested in K8-overexpressing mice and in cultured cells. Inclusion formation was examined using immune and conventional electron microscopy (EM). Bortezomib induced MDB-like inclusions composed of keratins, ubiquitin, and p62 in cultured cells. Short-term exposure to bortezomib induced similar inclusions in K8-overexpressing but not in nontransgenic mice, without causing liver injury. In bortezomib-treated mice, autophagy was activated in hepatocytes as determined by EM and biochemical analysis. Further activation of autophagy by rapamycin (Rap) decreased the number of inclusions in bortezomib-treated K8 transgenic mice significantly. Rap also led to resorption of spontaneously formed MDBs in aging K8-overexpressing mice. Immune EM demonstrated K8-positive and ubiquitin-positive structures in autophagic vacuoles in the mouse liver. Conclusion: PIs alone are sufficient to induce MDBs in susceptible animals, while Rap-mediated activation of autophagy prevents MDB formation and causes MDB resorption. These findings suggest that some patients treated with PIs may become predisposed to MDB formation. Autophagy provides a potential cellular mechanism for the resorption of cytoplasmic inclusions. (HEPATOLOGY 2008.) [source] Ion channels in toxicologyJOURNAL OF APPLIED TOXICOLOGY, Issue 6 2010Iván Restrepo-Angulo Abstract Ion channels play essential roles in human physiology and toxicology. Cardiac contraction, neural transmission, temperature sensing, insulin release, regulation of apoptosis, cellular pH and oxidative stress, as well as detection of active compounds from chilli, are some of the processes in which ion channels have an important role. Regulation of ion channels by several chemicals including those found in air, water and soil represents an interesting potential link between environmental pollution and human diseases; for instance, de novo expression of ion channels in response to exposure to carcinogens is being considered as a potential tool for cancer diagnosis and therapy. Non-specific binding of several drugs to ion channels is responsible for a huge number of undesirable side-effects, and testing guidelines for several drugs now require ion channel screening for pharmaceutical safety. Animal toxins targeting human ion channels have serious effects on the population and have also provided a remarkable tool to study the molecular structure and function of ion channels. In this review, we will summarize the participation of ion channels in biological processes extensively used in toxicological studies, including cardiac function, apoptosis and cell proliferation. Major findings on the adverse effects of drugs on ion channels as well as the regulation of these proteins by different chemicals, including some pesticides, are also reviewed. Association of ion channels and toxicology in several biological processes strongly suggests these proteins to be excellent candidates to follow the toxic effects of xenobiotics, and as potential early indicators of life-threatening situations including chronic degenerative diseases. Copyright © 2010 John Wiley & Sons, Ltd. [source] Gene expression profiling of aging in multiple mouse strains: identification of aging biomarkers and impact of dietary antioxidantsAGING CELL, Issue 4 2009Sang-Kyu Park Summary We used DNA microarrays to identify panels of transcriptional markers of aging that are differentially expressed in young (5 month) and old (25 month) mice of multiple inbred strains (129sv, BALB/c, CBA, DBA, B6, C3H and B6C3F1). In the heart, age-related changes of five genes were studied throughout the mouse lifespan: complement component 4, chemokine ligand 14, component of Sp100-rs, phenylalanine hydroxylase and src family associated phosphoprotein 2. A similar analysis in the brain (cerebellum) involved complement component 1q (alpha polypeptide), complement component 4, P lysozyme structural, glial fibrillary acidic protein and cathepsin S. Caloric restriction (CR) inhibited age-related expression of these genes in both tissues. Parametric analysis of gene set enrichment identified several biological processes that are induced with aging in multiple mouse strains. We also tested the ability of dietary antioxidants to oppose these transcriptional markers of aging. Lycopene, resveratrol, acetyl- l -carnitine and tempol were as effective as CR in the heart, and ,-lipoic acid and coenzyme Q10 were as effective as CR in the cerebellum. These findings suggest that transcriptional biomarkers of aging in mice can be used to estimate the efficacy of aging interventions on a tissue-specific basis. [source] Proteomic analysis of membrane rafts of melanoma cells identifies protein patterns characteristic of the tumor progression stagePROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 22 2008Frédérique Baruthio Abstract The molecular mechanisms controlling the progression of melanoma from a localized tumor to an invasive and metastatic disease are poorly understood. In the attempt to start defining a functional protein profile of melanoma progression, we have analyzed by LC-MS/MS the proteins associated with detergent resistant membranes (DRMs), which are enriched in cholesterol/sphingolipids-containing membrane rafts, of melanoma cell lines derived from tumors at different stages of progression. Since membrane rafts are involved in several biological processes, including signal transduction and protein trafficking, we hypothesized that the association of proteins with rafts can be regulated during melanoma development and affect protein function and disease progression. We have identified a total of 177 proteins in the DRMs of the cell lines examined. Among these, we have found groups of proteins preferentially associated with DRMs of either less malignant radial growth phase/vertical growth phase (VGP) cells, or aggressive VGP and metastatic cells suggesting that melanoma cells with different degrees of malignancy have different DRM profiles. Moreover, some proteins were found in DRMs of only some cell lines despite being expressed at similar levels in all the cell lines examined, suggesting the existence of mechanisms controlling their association with DRMs. We expect that understanding the mechanisms regulating DRM targeting and the activity of the proteins differentially associated with DRMs in relation to cell malignancy will help identify new molecular determinants of melanoma progression. [source] The impact of vector-mediated neutrophil recruitment on cutaneous leishmaniasisCELLULAR MICROBIOLOGY, Issue 9 2009Nathan C. Peters Summary The dynamic process of pathogen transmission by the bite of an insect vector combines several biological processes that have undergone extensive co-evolution. Whereas the host response to an insect bite is only occasionally confronted with the parasitic pathogens that competent vectors might transmit, the transmitted parasites will always be confronted with the acute, wound-healing response that is initiated by the bite itself. Invariably, this response involves neutrophils. In the case of Leishmania, infection is initiated in the skin following the bite of an infected sand fly, suggesting that Leishmania must possess some means to survive their early encounter with recruited neutrophils at the bite site. Here, we review the literature regarding the impact of neutrophils on the outcome of infection with Leishmania, with special attention to the role of the sand fly bite. [source] Transcriptional control and gene silencing in Plasmodium falciparumCELLULAR MICROBIOLOGY, Issue 10 2008Bradley I. Coleman Summary Infection with the apicomplexan parasite Plasmodium falciparum is associated with a high burden of morbidity and mortality across the developing world, yet the mechanisms of transcriptional control in this organism are poorly understood. While P. falciparum possesses many of the characteristics common to eukaryotic transcription, including much of the canonical machinery, it also demonstrates unique patterns of gene expression and possesses unusually AT-rich intergenic sequences. Importantly, several biological processes that are critical to parasite virulence involve highly regulated patterns of gene expression and silencing. The relative scarcity of transcription-associated proteins and specific cis -regulatory motifs recognized in the P. falciparum genome have been thought to reflect a reduced role for transcription factors in transcriptional control in these parasites. New approaches and technologies, however, have led to the discovery of many more of these elements, including an expanded family of DNA-binding proteins, and a re-assessment of this hypothesis is required. We review the current understanding of transcriptional control in P. falciparum, specifically highlighting promoter-driven and epigenetic mechanisms involved in the control of transcription initiation. [source] | ||||||||||||||||