Electronic Journal of Pathology and Histology - Volume 6, issue 1

Authors: Kayser, Klaus

Article Type: Other

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Citation: Electronic Journal of Pathology and Histology, vol. 6, no. 1, pp. 01-01, 2000

Authors: Villalobo, Antonio

Article Type: Research Article

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Citation: Electronic Journal of Pathology and Histology, vol. 6, no. 1, pp. 02-02, 2000

Authors: Benaim, Gustavo | Cervino, Vincenza

Article Type: Research Article

Abstract: Cell signaling in trypanosomatids has recently became a major field of research interest. Calcium has been recognized as a pivotal second messenger in many different functions in these parasites from cell growth and differentiation to host cell invasion. Its function as messenger has been related to other cell signaling systems where a close connection is apparent. The homeostasis of the intracellular calcium concentration, which enable its role as a messenger is the consequence of the coordinated …function of different transport systems located in the plasma membrane as well as in intracellular organelles. The general mechanisms for calcium regulation characteristic of the host cell are also present in this parasite with some interesting differences. The Ca2+ receptor protein calmodulin, albeit a well conserved protein throughout evolution, is present in high amounts in these parasites and share both similarities and distinct features when compared to mammals. The evidences accumulated up to day prompt for further investigation looking for differences between calcium homeostasis in trypanosomes and humans in order to develop a rational therapy, which is missing in all the illness caused by these hemoflagellates. Show more

Keywords: trypanosomatids, calmodulin, calcium homeostasis, therapy

Citation: Electronic Journal of Pathology and Histology, vol. 6, no. 1, pp. 03-03, 2000

Authors: Benguria, Alberto

Article Type: Research Article

Abstract: Aging research is entering in an exciting moment due to the identification of genes and pathways that modulate this process. This has been elucidated in lower eukaryotic organisms, mainly in yeast and in the nematode Caenorhabditis elegans. These studies have suggested that metabolic capacity, efficiency of stress responses and genetic regulation play an important role in determining life span, and signal transduction pathways clearly regulate these processes. Similar pathways exist in mammals and some of them …might also regulate their pace of aging. Show more

Keywords: Aging, nematodes, yeast, Drosophila melanogaster, growth factor

Citation: Electronic Journal of Pathology and Histology, vol. 6, no. 1, pp. 04-04, 2000

Authors: Galea, Elena | Bhat, Narayan R. | Feinstein, Douglas L.

Article Type: Research Article

Abstract: The enzyme nitric oxide synthase 2 (NOS2, or inducible NOS) is expressed by numerous cell types during inflammatory reactions in vivo and in vitro. The NO derived from NOS2 exerts beneficial actions such as the elimination of microorganisms, the reduction of thrombosis, and the increase of blood supply to injured tissues. However, NO released in excess can cause tissue damage, contributing to diseases like septic shock, rheumatoid arthritis, cerebral ischemia, multiple sclerosis, and diabetes. It is …well established that induction of the NOS2 protein by inflammatory stimuli is primarily regulated at the level of gene transcription, and that the interaction of the transcription factor NFkB and its inhibitory protein, IkB, play a central role in this process. In addition, recent pharmacological evidence implicates the mitogen activated protein kinase (MAPK) pathways as a second key mediator of the cytokine-induced transcription of NOS2. In turn, the induction of the NOS2 gene can be either inhibited or potentiated, depending on the cell type, by cyclic AMP-dependent pathways, acting via transcription factors like CREB, NFkB and C/EBP. Finally, the heat shock response has recently emerged as a second potent means of suppressing both the cytokine and endotoxin-dependent activation of NOS2 transcription. The mechanism responsible for this suppression appears to be the prevention of NFkB activation. These observations suggest that the transcription of the NOS2 gene is tightly regulated by several cascades of cytoplasmic and nuclear reactions, thus providing a wide array of biological and therapeutical targets to control the production of NO to avoid its detrimental actions. Show more

Keywords: cyclic AMP, CREB, C/EBP, cytokines, endotoxin, gene expression, heat shock, promoter, mRNA, MAP kinases, NFkB, transcription factors,

Citation: Electronic Journal of Pathology and Histology, vol. 6, no. 1, pp. 05-05, 2000

Authors: Kuo, Tuan H. | Zhu, Liping

Article Type: Research Article

Abstract: Despite many years of intensive studies, the role of intracellular calcium homeostasis in the regulation of cell death is still unclear and controversial. Partly, this is due to the lack of an understanding of cellular Ca2+ signaling processes in an integrated manner. While earlier studies on Ca2+ signaling have emphasized the interaction between the plasma membrane and the endoplasmic reticulum (ER) compartments, more recent work from several laboratories have clearly indicated the active participation of mitochondria …in this intracellular Ca2+ network. It has now becoming recognized that mitochondria provide an important missing link in the mechanism whereby Ca2+ regulates apoptosis and necrosis. The purpose of this review is to summarize the role of mitochondria in calcium homeostasis and in the control of cell death. Apoptotic and nonapoptotic cell death is attracting enormous attention in virtually every aspect of modern pathology. While alterations in intracellular calcium homeostasis are commonly observed during apoptosis, the mechanism whereby calcium might regulate the apoptosis is still poorly understood. Previous studies from many laboratories have stressed the elevated cytoplasmic Ca2+ concentration (calcium overload) as a cause of cell injury. Excessive Ca2+ influx has been recognized as a key component of ischaemic brain damage for many years. Based on these findings, drugs such as the voltage-dependent calcium channel antagonists (nimodipine and flunarizine) have been tested in human clinical trials. However, the results from completed trials have been disappointing [25]. The lack of efficacy with these drugs in reducing neuronal cell injury has raised questions on the notion that Ca2+ overload is a pathogenic principle during ischaemic injury [25]. The status of Ca2+ homeostasis in cells undergoing apoptosis has not been clearly delineated. In some cases, elevated cytoplasmic Ca2+ (Cac) has been observed, and this condition has been suggested as a likely candidate to activate certain parts of the apoptosis cascade, such as the endonuclease responsible for internucleosomal DNA cleavage [reviewed in 28]. However, apoptosis of cultured neurons is attenuated by increasing Cac via the activation of voltage-gated Ca2+ channels [15, 22]. It appears that either too much or too little Ca2+ can pose problems for cell survival. The purpose of this review is to provide some recent advances on the role of Ca2+ homeostasis in the regulation of apoptosis and necrosis. Related issues are addressed in previous reviews [9, 28, 12]. Show more

Keywords: Ca2+ homeostasis, apoptosis, mitochondria, permeability transition

Citation: Electronic Journal of Pathology and Histology, vol. 6, no. 1, pp. 06-06, 2000

Authors: Li, Hongbing | Palomo-Jiménez, Paloma I. | Ruano, María José | Villalobo, Antonio

Article Type: Research Article

Abstract: The epidermal growth factor receptor (EGFR) is a plasma membrane tyrosine kinase that belongs, together with other three related members, to the ErbB family of receptors. These receptors share a large group of polypeptide ligands, that induce homodimerization or heterodimerization among themselves, and the activation of their intrinsic tyrosine kinases followed by their transphosphorylation. The active phosphorylated receptors generate a series of signaling events conducted to initiate cell proliferation, differentiation and/or antiapoptotic …responses. In this short review it will be analysed some major signaling pathways initiated by EGFR activation, the regulatory mechanisms controlling its tyrosine kinase activity, some of which are mediated by the calcium signal generated by the own receptor, and its downregulation and internalisation. Moreover, the cross-talk between the EGFR and other ErbB family members, and between the EGFR and other non-related receptors, will be described. Finally, the importance of this receptor in embryogenesis and in proliferative processes in adult individuals will be analysed by the description of some genetic alterations that result in the occurrence of important foetal malformations and the generation of cancerous tumors. Show more

Keywords: Epidermal growth factor, signal transduction, desensitisation, transactivation

Citation: Electronic Journal of Pathology and Histology, vol. 6, no. 1, pp. 07-07, 2000

Authors: Maki, Masatoshi

Article Type: Research Article

Abstract: ALG-2 is a new 22 kDa intracellular calcium-binding protein involved in apoptosis. Forced reduction of ALG-2 gene expression makes the antisense-DNA-transfected T cell-lines resistant to apoptosis induced by various stimuli. ALG-2 belongs to the penta-EF-hand protein family which includes the calpain small subunit, sorcin, grancalcin and peflin in mammals. The family members contain five EF-hand motifs in their C-termini. The N-terminal regions are rich in glycine and hydrophobic residues. ALG-2 binds to …a newly identified protein named Alix or AIP1. The overall structure of Alix/AIP1 is similar to Xenopus oocyte phosphoprotein Xp95, Aspergillus nidulans alkaline adaptation factor PalA and the budding yeast protein named BRO1 involved in a MAP kinase cascade. A similar sequence is also found in a hypothetical protein of plant. All these proteins contain a potential tyrosine-phosphorylation site and a few PXXP motifs (SH3-binding sites), suggesting involvement of ALG-2 or its homologs in basic signal transduction common in all eukaryotic cells. Show more

Keywords: apoptosis, ALG-2, signal transduction

Citation: Electronic Journal of Pathology and Histology, vol. 6, no. 1, pp. 08-08, 2000

Authors: Monteith, Gregory R. | Roufogalis, Basil D.

Article Type: Research Article

Abstract: The importance of calcium in regulating vascular tone has been understood for many years, and has made calcium the focus of many researchers studying hypertension. The recent advances in techniques to assess cytosolic free Ca2+ in living cells using fluorescence, and advances in molecular biology techniques have expanded our understanding of Ca2+ regulation. In this review we provide a brief overview of calcium regulation in vascular smooth muscle and focus on the regulation of calcium in …hypertension. We pay particular attention to studies in animal models of hypertension and studies examining active transporters of calcium in vascular smooth muscle. Show more

Keywords: calcium, hypertension, Ca2+, ATPases, vascular smooth muscle, intracellular calcium

Citation: Electronic Journal of Pathology and Histology, vol. 6, no. 1, pp. 09-09, 2000

Authors: O'Brian, Catherine A. | Stewart, Jubilee R. | Ward, Nancy E. | Bergman, Philip J.

Article Type: Research Article

Abstract: Protein kinase C (PKC) is an extensive isozyme family that plays critical roles in cell growth regulation and differentiation and in specialized physiological processes such as neurotransmission. The regulation of PKC isozymes is complex not only due to the existence of isozyme-selective regulatory mechanisms but also due to the fact that multiple regulatory mechanisms may contribute to the governance of the function of a given isozyme. Most PKC isozymes require trans-phosphorylation by phosphoinositide-dependent …kinase-1 (PDK1) to become catalytically competent and stimulation by lipid cofactors (in some cases in conjunction with Ca2+) to be activated. At least two PKC isozymes, d and q, can be proteolytically converted in cells to lipid-independent activated forms that participate in cell signaling. In addition, evidence is now emerging that oxidative stimuli may induce PKC activation in cells under certain conditions via tyrosine phosphorylation of the isozymes, and that under other conditions the oxidants may inactivate PKC isozymes by oxidative modification of Cys residues in the catalytic domain. Isozyme-selective binding proteins that direct the localization of PKC isozymes offer yet another level of regulatory control over PKC signaling. Show more

Keywords: protein kinase C, isoenzymes, trans-phosphorylation

Citation: Electronic Journal of Pathology and Histology, vol. 6, no. 1, pp. 10-10, 2000

Authors: Pol, Albert | Calvo, Maria | Pons, Mònica | Peiró, Sandra | Andrés, Noemí | Tebar, Francesc | Enrich, Carlos

Article Type: Research Article

Abstract: Hormones and growth factors regulate cell metabolism, growth, differentiation and mitogenesis by interacting with plasma membrane located receptors. Upon ligand binding receptors are rapidly internalised into a series of complex membranes system collectively called endocytic compartment. Detailed studies on a number of receptor tyrosine kinases suggest that internalisation, rather than simply serving as a mechanism for uptake, may also allow for selected and regulated signal transduction from intracellular compartments. Although signal transduction …is often credited with being a cascade of interactions initiated at the plasma membrane but exerting its final effects in the nucleus, now it has become clear that certain signal-transduction pathways affect membrane trafficking. Show more

Keywords: Hepatocyte, endocytic compartment, epidermal growth factor, endosome

Citation: Electronic Journal of Pathology and Histology, vol. 6, no. 1, pp. 11-11, 2000

Authors: Quintanilla, Miguel | Frontelo, Pilar | Iglesia, Maite

Article Type: Research Article

Abstract: During malignant progression tumor cells acquire the ability to invade surrounding tissues and metastasize to distant organs. In epithelial tumors, malignancy correlates with loss of the epithelial phenotype and gain of fibroblastic characteristics. The mouse skin system has been extensively used to study molecular and cellular events leading to initiation, promotion and progression of tumorigenesis. In the mouse skin carcinogenesis model, initiated keratinocytes containing a carcinogen-induced H-Ras oncogene mutation give rise to …benign papillomas, some of which progress to squamous cell carcinomas. Late stages of carcinogenesis are associated with the development of highly invasive and metastatic spindle carcinomas. In vitro and in vivo studies using this and other epithelial cell systems have shown that TGF-b1 induces the squamous-spindle carcinoma transition, and that an activated H-Ras oncogene cooperates with TGF-b1 to stimulate malignancy of carcinoma cells. Signaling events regulating migratory and invasive cell responses are less well characterized than those leading to uncontrolled cell proliferation. In this article, we discuss possible signaling pathways involved in malignant progression of mouse skin tumors. Show more

Keywords: skin tumors, carcinogenesis, H-Ras mutation, TGF-b

Citation: Electronic Journal of Pathology and Histology, vol. 6, no. 1, pp. 12-12, 2000

Authors: Zeng, Fu-Yue

Article Type: Research Article

Abstract: G protein-coupled receptors represent one of the largest families of cell surface receptors in nature. These receptors play fundamental roles in diverse physiological processes such as neurotransmission, cellular metabolism, cell differentiation and growth as well as immune response. In response to extracellular ligands, G protein-coupled receptors specifically interact with heterotrimeric G proteins that can then activate or inhibit effector enzymes, ultimately leading to the physiological response. Biochemical and mutational studies have revealed …the molecular mechanisms of ligand-receptor interaction, receptor activation and receptor-G protein coupling selectivity. In the last few years, increasing evidence suggested that G protein-coupled receptor are also involved in other novel signaling pathways in addition to classical G protein-mediated pathways. This review will briefly summarize recent studies on structural and functional aspects of G protein-coupled receptors with emphasis on molecular mechanisms of receptor activation. Show more

Keywords: G protein-coupled receptors, ligand-receptor interaction, receptor structure, receptor activation

Citation: Electronic Journal of Pathology and Histology, vol. 6, no. 1, pp. 13-13, 2000

Authors: Zylinska, Ludmila

Article Type: Research Article

Abstract: During the last decade the mechanisms of Ca2+ regulation in the brain have been extensively investigated in a variety of neural cells. These investigations demonstrate that intraneuronal Ca2+ participate in the multiple controls of important neural functions, like excitability, neurotransmitters release or long-term changes in synaptic efficacy. Moreover, there is a significant number of data confirming that the impairment of calcium homeostasis is closely linked with aging and several brain disorders. The …plasma membrane Ca2+-ATPase (PMCA) is a ubiquitously expressed protein, which constitutes a high affinity system extruding Ca2+ outside the cell and maintains the intracellular Ca2+ in the submicromolar range in a resting state. In neuronal tissues more than 26 transcripts of the four separate PMCA genes are distributed in a region specific manner. Differences in the structure and localization of PMCA variants are thought to correlate with specific regulatory properties and may have consequences for proper Ca2+ signaling or for the response to the brain malfunction. Below some new aspects of the Ca2+-ATPase modulation in physiological and pathological conditions will be discussed which may influence neuronal calcium signaling. Show more

Keywords: plasma membrane Ca2+-ATPase, brain, regulation, pathology, calcium homeostasis

Citation: Electronic Journal of Pathology and Histology, vol. 6, no. 1, pp. 14-14, 2000

Authors: Kayser, Klaus

Article Type: Book Review

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Citation: Electronic Journal of Pathology and Histology, vol. 6, no. 1, pp. 15-15, 2000

Authors: Kayser, Klaus

Article Type: Book Review

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Citation: Electronic Journal of Pathology and Histology, vol. 6, no. 1, pp. 16-16, 2000

Authors: Kayser, Klaus

Article Type: Book Review

Keywords:

Citation: Electronic Journal of Pathology and Histology, vol. 6, no. 1, pp. 17-17, 2000