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Pathological Events (pathological + event)
Selected AbstractsIntraneuronal APP/A, Trafficking and Plaque Formation in ,-Amyloid Precursor Protein and Presenilin-1 Transgenic MiceBRAIN PATHOLOGY, Issue 3 2002Oliver Wirths Neuropil deposition of ,-amyloid peptides A,40 and A,42 is believed to be the key event in the neurodegenerative processes of Alzheimer's disease (AD). Since A, seems to carry a transport signal that is required for axonal sorting of its precursor ,-amyloid precursor protein (APP), we studied the intraneuronal staining profile of A, peptides in a transgenic mouse model expressing human mutant APP751 (KM670/671NL and V717I) and human mutant presenilin-1 (PS-1 M146L) in neurons. Using surface plasmon resonance we analyzed the A, antibodies and defined their binding profile to APP, A,40 and A,42. Immunohistochemical staining revealed that intraneuronal A,40 and A,42 staining preceded plaque deposition, which started at 3 months of age. A, was observed in the somatodendritic and axonal compartments of many neurons. Interestingly, the striatum, which lacks transgenic APP expression harbored many plaques at 10 months of age. This is most likely due to an APP/A, transport problem and may be a model region to study APP/A, trafficking as an early pathological event. [source] Development of a CE-MS method to analyze components of the potential biomarker vascular endothelial growth factor 165ELECTROPHORESIS, Issue 13 2009Angel Puerta Abstract The vascular endothelial growth factor 165 (VEGF165) is the predominant form of the complex VEGF-A family. Its angiogenic effect is involved in many physiological and pathological events. For this reason, its roles as a potential biomarker and as a therapeutic drug have been considered. Nevertheless, very little is known about the existence of different forms of VEGF165 arising from glycosylation and potentially from other PTMs. This aspect is important because different forms may differ in biological activity (therapeutic drug application) and the pattern of the different forms can vary with pathological changes (biomarker application). In this work a CE-MS method to separate up to seven peaks containing, at least, 19 isoforms of intact VEGF165 is described. Comparison between human VEGF165 expressed in a glycosylating system, i.e. insect cells, and in a non-glycosylating system, i.e. E. coli cells, has been carried out. The method developed provides structural information (mass fingerprint) about the different forms of VEGF165 and after the deconvolution and the analysis of the MS spectra, PTMs pattern of VEGF165 including glycosylation and loss of amino acids at the N- and C-terminus was identified. Glycans involved in PTMs promoting different glycoforms observed in the CE-MS fingerprint were confirmed by MALDI-MS after deglycosylation with peptide N-glycosidase F. This approach is a starting point to study the role of VEGF165 as a potential biomarker and to perform quality control of the drug during manufacturing. To our knowledge this is the first time that a CE-MS method for the analysis of VEGF165 has been developed. [source] P2Y1 receptor signaling enhances neuroprotection by astrocytes against oxidative stress via IL-6 release in hippocampal culturesGLIA, Issue 3 2009Takumi Fujita Abstract Cell survival is a critical issue in the onset and progression of neurodegenerative diseases and following pathological events including ischemia and traumatic brain injury. Oxidative stress is the main cause of cell damage in such pathological conditions. Here, we report that adenosine 5,-triphosphate (ATP) protects hippocampal astrocytes from hydrogen peroxide (H2O2)-evoked oxidative injury in astrocyte monocultures. The effect of ATP was prevented by a selective antagonist of or siRNAs against P2Y1R. Interestingly, in astrocyte-neuron cocultures, ATP also produced neuroprotective effects against H2O2 -evoked neuronal cell death, whereas ATP did not produce any neuroprotective effects in monocultures. The ATP-induced neuroprotection in cocultures was completely inhibited by silencing of astrocytic P2Y1R expression, indicating that ATP acts on astrocytes and enhances their neuroprotective functions by activating P2Y1R. Furthermore, this neuroprotective effect was mimicked by applying conditioned medium from astrocytes that had been stimulated by ATP, implying an involvement of diffusible factors from astrocytes. We found that, in both purified astrocyte cultures and astrocyte-neuronal cocultures, ATP and the P2Y1R agonist 2-methylthioadenosine 5, diphosphate (2MeSADP) induced the release of interleukin-6 (IL-6), but this did not occur in neuron monocultures. Moreover, exogenous IL-6 produced a neuroprotective effect, and the neuroprotection induced by P2Y1R-stimulated astrocytes was prevented in the presence of an anti-IL-6 antibody. Taken together, these results suggest that P2Y1R-stimulated astrocytes protect against neuronal damage induced by oxidative stress, and that IL-6 is a crucial signaling molecule released from astrocytes. Thus, activation of P2Y1R in astrocytes may rescue neurons from secondary cell death under pathological conditions. © 2008 Wiley-Liss, Inc. [source] Peroxynitrite and nitrosoperoxycarbonate, a tightly connected oxidizing-nitrating couple in the reactive nitrogen-oxygen species family: new perspectives for protection from radical-promoted injury by flavonoidsJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 12 2007Radmila Pavlovic Peroxynitrite is the product of the reaction of nitric oxide with superoxide radical and is implicated in the pathogenesis of a wide variety of human diseases, being responsible for in-vivo oxidation/nitration events. Nitrosoperoxycarbonate anion, formed by the interaction of peroxynitrite with CO2/bicarbonate at physiological concentrations, provides a new interpretation of oxidative/nitrative processes formerly attributed to peroxynitrite. The aim of this review is to summarize the chemistry and biology of peroxynitrite and radical species related to nitrosoperoxycarbonate anion, as well as the information available regarding the molecular mechanisms that determine and regulate radical-promoted injury by the two tightly connected species at physiological concentrations. Interception of carbonate and nitro radicals produced by interaction of peroxynitrite with CO2/bicarbonate, as in-vivo prevention of pathological events, creates new perspectives for the evaluation of safe scavengers of oxidative/nitrative stress at the physiological level. In this respect, natural products such as flavonoids hold a preeminent position among the vast array of compounds endowed with such properties. [source] Carbohydrate recognition by boronolectins, small molecules, and lectinsMEDICINAL RESEARCH REVIEWS, Issue 2 2010Shan Jin Abstract Carbohydrates are known to mediate a large number of biological and pathological events. Small and macromolecules capable of carbohydrate recognition have great potentials as research tools, diagnostics, vectors for targeted delivery of therapeutic and imaging agents, and therapeutic agents. However, this potential is far from being realized. One key issue is the difficulty in the development of "binders" capable of specific recognition of carbohydrates of biological relevance. This review discusses systematically the general approaches that are available in developing carbohydrate sensors and "binders/receptors," and their applications. The focus is on discoveries during the last 5 years. © 2009 Wiley Periodicals, Inc. Med Res Rev, 30, No. 2, 171,257, 2010 [source] Experimental superficial candidiasis on tissue modelsMYCOSES, Issue 4 2010J. A. M. S. Jayatilake Summary Candida species are common pathogens causing superficial mycoses primarily affecting the mucosa and the skin in humans. Crucial steps during pathogenesis of superficial candidiasis comprise fungal adhesion, colonisation and subsequent penetration of the respective tissues. Exploring these pathological events and perhaps fungal and tissue responses towards drug treatment is imperative in the management of this infection. Unfortunately, pathological biopsies of superficial candidiasis do not exhibit the early changes in the host,pathogen interaction as the tissues are already invaded by the fungi. In vivo experimental assessments of pathological processes of superficial candidiasis are also limited because of the difficulties in providing reproducible and comparable conditions in the host environment. Conversely, in vitro models have helped studying fungal,host interactions under more defined and controlled conditions. Some common in vitro models used to simulate superficial candidiasis are chick chorioallantoic membrane, mucosal explants and single layer or multiple layer cell cultures. Interestingly, these experimental approaches share advantages as well as disadvantages when compared with in vivo conditions. Hence, this review intends to discuss about the experimental superficial candidiasis produced in various tissue models and their advantages as well as disadvantages with a particular reference to further improvement of validity and reliability of such experiments. [source] Cytoplasmic Extracts from Adipose Tissue Stromal Cells Alleviates Secondary Damage by Modulating Apoptosis and Promotes Functional Recovery Following Spinal Cord InjuryBRAIN PATHOLOGY, Issue 3 2007Soo Kyung Kang Spinal cord injury (SCI) typically results from sustained trauma to the spinal cord, resulting in loss of neurologic function at the level of the injury. However, activation of various physiological mechanisms secondary to the initial trauma including edema, inflammation, excito-toxicity, excessive cytokine release and apoptosis may exacerbate the injury and/or retard natural repair mechanisms. Herein, we demonstrate that cytoplasmic extracts prepared from adipose tissue stromal cells (ATSCs) inhibits H2O2 -mediated apoptosis of cultured spinal cord-derived neural progenitor cells (NPCs) resulting in increased cell survival. The ATSC extracts mediated this effect by decreasing caspase-3 and c-Jun,NH2-terminal kinase (SAPK/JNK) activity, inhibiting cytochrome c release from mitochondria and reducing Bax expression levels in cells. Direct injection of ATSC extracts mixed with Matrigel into the spinal cord immediately after SCI also resulted in reduced apoptotic cell death, astrogliosis and hypo-myelination but did not reduce the extent of microglia infiltration. Moreover, animals injected with the ATSC extract showed significant functional improvement of hind limbs as measured by the BBB (Basso, Beattie and Bresnahan) scale. Collectively, these studies show a prominent therapeutic effect of ATSC cytoplasmic extracts on SCI principally caused by an inhibition of apoptosis-mediated cell death, which spares white matter, oligodendrocytes and neurons at the site of injury. The ability of ATSC extracts to prevent secondary pathological events and improve neurologic function after SCI suggests that extracts prepared from autologous cells harvested from SCI patients may have clinical utility. [source] Functional roles of N -glycans in cell signaling and cell adhesion in cancerCANCER SCIENCE, Issue 7 2008Yan-Yang Zhao Glycosylation is one of the most common post-translational modification reactions and nearly half of all known proteins in eukaryotes are glycosylated. In fact, changes in oligosaccharide structures are associated with many physiological and pathological events, including cell growth, migration, differentiation, tumor invasion, host,pathogen interactions, cell trafficking, and transmembrane signaling. Emerging roles of glycan functions have been highly attractive to scientists in various fields of life science as they open a field, "Functional Glycomics", that is a comprehensive study of the glycan structures in relation to functions. In particular, the N-glycans of signaling molecules including receptors or adhesion molecules are considered to be involved in cellular functions. This review will focus on the roles of glycosyltransferases involved in the biosynthesis of N-glycan branching and identification of cell surface receptors as their target proteins. We also suggest that the modulation of N-glycans of those receptors alters their important functions such as cell signaling and cell adhesion which are implicated in cancer invasion and metastasis. (Cancer Sci 2008; 99: 1304,1310) [source] | |||||||||||||