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EN
Metallothioneins are intracellular proteins binding metals. There proteins are involved in zinc and copper homeostasis as well as in organism detoxication of heavy metals. The induction of metallothioneins synthesis is caused not only by metal ions but also by the interleukins, by tumor necrosis factor and by glicocortycoids or the stressing factors. Metallothioneins prove the protective action in cadmium toxication and prevent interaction of cadmium with thiol groups -SH proteins. In neoplasms the increase of metallothionein level occurs both in tumors and in liver, the level of these proteins is correlated with the size of the tumor.
EN
The iron regulatory proteins (IRP1 and IRP2) are two cytoplasmic RNA-binding proteins involved in the mechanisms that control iron metabolism in mammalian cells. They modulate the expression of iron-related proteins at a post-transcriptional level by binding to specific iron regulatory elements (IREs) on their mRNAs. IRP-IRE interaction can block protein synthesis or stabilize the mRNA. At low intracellular iron concentration, IRPs bind to the IRE of ferritin or ferroportin mRNAs and block their translation. Direct interactions between IRPs and several IRE motifs stabilize transferrin receptor mRNA. The converse regulation of ferritin and TfR synthesis, being a consequence of the lack of binding of IRPs to IRE, occurs in cells with high iron level. Thus, IRP-mediated regulation rapidly restores the physiological level of iron during its deficiency as well as excess. The role of IRPs in maintaining the intracelluar iron balance has been relatively well characterized in numerous types of mammalian cells. However, the importance of IRPs in the regulation of systemic iron metabolism in mammals, particularly, in signaling between the cells which play major roles in body iron metabolism, such as duodenal enterocytes, reticuloendothelial macrophages, hepatocytes, and bone marrow precursors of red blood cells, is only beginning to be investigated. Several studies have shown that IRP2 is a predominant regulator of iron homeostasis in mice housed under standard conditions, thus limiting the impact of IRP1 on this metabolic pathway. Although IRP1-deficient mice do not display a strong pathological phenotype, a deletion of both IRPs is embryonic lethal. In addition, in vitro and in vivo studies have reported that nitric oxide (NO) and hydrogen peroxide (H2O2), which are produced during inflammation, are potent IRP1 regulators that mediate the disassembly of Fe-S cluster of IRP1. There is also an increasing evidence that NO and superoxide anion (O2 @!) may induce a strong down-regulation of IRP1 at the protein level and thus have an impact on the binding of IRP1 to IREs. All these data suggest a predominant role of IRP1 in the regulation of iron homeostasis under specific physiopathological conditions.
EN
Understanding the homeostatic mechanisms governing lymphocyte pools achieves critical importance as lymphocyte-targeted therapies expand in use and scope. The primacy of B lymphocyte stimulator (BLyS) family ligands and receptors in governing B lymphocyte homeostasis has become increasingly clear in recent years, affording insight into novel opportunities and potential pitfalls for targeted B cell therapeutics. Interclonal competition for BLyS-BR3 interactions determines the size of na?ve B cell pools and can regulate the stringency of selection applied as cells complete maturation. Thus one of the predicted consequences of ablative therapies targeting primary pools is relaxed negative selection. This suggests that BLyS levels and B cell reconstitution rates may serve useful prognostic roles and that BLyS itself might be targeted to circumvent relapse. Alternatively, manipulations that allow rare, minimally autoreactive specificities to survive and mature may lead to opportunities in cases where antibody-based vaccine development has heretofore been unsuccessful. BLyS family ligands and receptors also play a role in activated and memory B cell pools, suggesting they might likewise be targeted to promote or delete particular antigen-experienced subpopulations in a similar way.
EN
The mechanisms that maintain a pool of B cells that is adequately diverse yet devoid of pathogenic autoreactivity remain poorly understood. B cells complete maturation after migrating to the periphery, where they transit several intermediate developmental stages prior to recruitment into the long-lived primary pool. Since B lineage commitment is not coupled to peripheral B cell numbers and most mature peripheral B cells are quiescent, the sizes of mature peripheral compartments are primarily determined by the proportion of immature B cells that survive transit through later developmental stages, coupled with the longevity of mature B cells themselves. Compelling evidence indicates that the B cell antigen receptor (BcR) plays an essential role in all of these processes, but further findings indicate a similar role for the recently described tumor necrosis factor family member, B lymphocyte stimulator (BLyS). Signaling through the BLyS receptor, Bcmd/BR3, controls B cell numbers in two ways: by varying the proportion of cells that complete transitional B cell development, and by serving as the primary determinant of mature B cell longevity. The striking congruence of BcR- and BLyS-mediated effects on B cell selection and survival suggests these pathways may be related. The recent discovery that BcR signaling is selectively coupled to Bcmd/BR3 expression links BcR- and BLyS-mediated activities in transitional and mature B cells, suggesting specificity-based selection and survival may be mechanistically similar processes.
EN
Iron is a key component of many reactions in the human body, and by virtue of its ability to accept and donate electrons, it is required for a variety of normal cellular functions and is vital for proper growth and development. However, natural iron is rather insoluble and excess of iron is harmful since it can catalyze the formation of oxygen radicals. Fortunately, there are also mechanisms for protecting human body from excess 'free' iron. This is particularly important, given the fact that humans have very limited capacity to excrete iron. Therefore, cells have developed mechanisms to improve the solubility of iron to control intracellular iron concentrations at the point of iron absorption in the small intestine and other tissues. Since the described process is highly complex, a profound understanding of all the relationships occurring among its components is possible when a systems approach is applied to its analysis.
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issue 3-4
181-189
EN
Stress, a state of threatened homeostasis, may be induced by various physical or psychological factors (stressors), including antigenic stimulation. Stressful experiences may affect both physical/psychological well being and immune functioning of humans and animals; the ongoing immune reaction may affect other physiological functions and psychological comfort. The molecular basis of these effects involves a network of multidirectional signalling and feedback regulations of neuroendocrine- and immunocyte-derived mediators. The consecutive stages of the multistep immune reactions might be either inhibited or enhanced owing to the previous and/or parallel stress experiences, depending on the kind of stressor and the animal species, strain, gender, or age. Therefore, the final results of stress-induced alteration of immune reactions are difficult to predict. The effect of a particular stressor on immune functions varies according to the previous stress experience of the individual (e.g. social confrontation, sterile saline injection) while various stressors may act in the same or in opposite ways on the same immune parameter. In general, the efficacy of immune response depends on the neuroendocrine environment on which it is superimposed. Conversely, neural and endocrine responses depend on the concurrent immune events upon which they are superimposed. It seems that the consequences of stress on the immune functioning are generally adaptive in the short run but can be damaging when stress is chronic.
EN
Regulation of T cell homeostasis is critical for maintaining normal immune function. An imbalance in T cell proliferation can result in disorders ranging from cancer and autoimmunity to immunodeficiencies. Full activation of T cells requires three sequential signals, where signal 3, which is delivered by multiple cytokines, regulates proliferation, differentiation, and survival/death. Signaling from cytokines through their receptors is primarily delivered by two molecular families, namely Janus tyrosine kinases (JAKs) and signal transducers and activators of transcription (STATs). Invaluable knowledge about JAKs and STATs has arisen from studies of mice made genetically deficient in these molecules, analyses of tumor models, and studies of expression patterns by proteomics/genomics, which all have begun to define the role of JAKs and STATs in survival versus apoptosis. These findings also have suggested ways in which JAKs and STATs may be manipulated for therapeutic intervention in lymphoid-derived diseases. This review seeks to focus on the role of JAK tyrosine kinases and STAT transcription factors in mediating the lymphocyte life cycle and how they might be manipulated for therapeutic applications.
EN
Recent studies have uncovered many aspects of the repair processes that follow airway epithelial injury. Although the repair process has common elements among various epithelia, such as the ones lining the airways, skin, and gut, there are differences based on their diverse functions. Whenever possible, similarities are pointed out that could help researchers further investigate their application to airway epithelia, although it would be beyond the scope of this review to cover the processes that may occur during the repair of all types of epithelia. In general, five major steps are involved in the recovery of airway epithelia from injury: 1) epithelial cells migrate to cover denuded areas within minutes, and certain proteins, such as the trefoil factor family proteins, are crucial to this process; 2) epithelial cells start to proliferate in order to replace injured cells and to differentiate to establish squamous or mucous cell metaplasia; 3) because more epithelial cells are present after proliferation, some of the cells must be discarded to restore the epithelium to the original condition; 4) once the cell numbers have been reduced to those found in unexposed individuals, the normal proportions of cell types are restored; 5) finally, studies from exposures of rats to ozone show that epithelial cells can adapt and develop a memory of the chronic exposure to which they were exposed. This adaptation allows the epithelium to respond quickly, thus minimizing further injury. Although the molecular mechanisms involved in these major steps of the recovery process are largely unknown, disruption of these steps clearly causes the permanent changes observed in diseases such as asthma, chronic bronchitis, and cancer; therefore, extensive research in these areas may provide ideas for novel therapies.
EN
The aim of the presented work was to study the effects of changes of endogenous indole-3-acetic acid (IAA) metabolizm on in vitro shoot proliferation and rhizogenesis of transgenic strawberry shoots carrying maize IAA-glucose synthase gene (iaglu). Four iaglu-transformed strawberry clones and nontransformed 'Kaster' shoots served as a plant material for the study. The analysis of free and conjugated IAA level in leaves of transgenic and control strawberry plants showed that iaglu-containing strawberry clones had significantly higher level of ester conjugated IAA, but the level of free hormone was only slightly decreased or comparable to the control plants. iaglu-transformed clones had significantly higher proliferation rate and formed more roots than the control shoots. One of the iaglu-transformed clones had significantly shorter and other two ? longer roots than the control plantlets.
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