Signal transduction最新文献

{"title":"Protective role of thioredoxin‐1 in cardiovascular systems","authors":"J. Haendeler","doi":"10.1002/SITA.200500064","DOIUrl":"https://doi.org/10.1002/SITA.200500064","url":null,"abstract":"The thioredoxin-1 (Trx-1) system consists of two oxidoreductases, the thioredoxin-reductase and Trx-1. Trx-1 is a ubiquitously expressed oxidoreductase. The cellular functions of Trx-1 are wide range. They include protein disulfide reduction, DNA synthesis, protection from apoptosis, redox regulation of a variety of proteins transcription factors and reduction of H2O2, respectively. This review will first focus on the essential role for Trx-1 in different cardiovascular cells, namely smooth muscle cells, endothelial cells and cardiomyocytes. Thereby, the review will demonstrate the predominant role of Trx-1 to limit oxidative stress directly due to reactive oxygen species scavenging and by protein-protein interaction with key signaling molecules. Furthermore, the review will focus on important in vivo studies showing a protective role of Trx-1 in different cardiovascular diseases. Thus, the Trx system and Trx-1 could be important future targets to develop clinical therapies for cardiovascular disorders.","PeriodicalId":88702,"journal":{"name":"Signal transduction","volume":"15 2","pages":"314-321"},"PeriodicalIF":0.0,"publicationDate":"2005-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/SITA.200500064","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50950585","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Signals, receptors, and cytokines involved in the immunomodulatory and anti-inflammatory properties of apoptotic cells","authors":"B. Fürnrohr, A. Sheriff, L. Munoz, H. Briesen, V. Urbonaviciute, K. Neubert, J. Kalden, M. Herrmann, R. Voll","doi":"10.1002/SITA.200500071","DOIUrl":"https://doi.org/10.1002/SITA.200500071","url":null,"abstract":"Cell death can occur controlled by apoptosis or rather uncontrolled by necrosis. The decision to initiate an inflammatory response has to be made for dying cells, which arise by hundreds of billions each day. They carry valuable information with respect to the possible influence of pathogens. Apoptosis and the swift phagocytosis of dying cells by macrophages and neighboring tissue cells act together to remove supernumerary, dangerous, or damaged cells. Apoptosis, in contrast to necrosis, normally does not induce inflammation or organ damage. Apoptotic cells maintain their membrane integrity for a relatively long time, thereby preventing the release of tissue damaging contents and proinflammatory mediators. In addition, early recognition and efficient, non-inflammatory removal of the apoptotic cells essentially contribute to preventing an inflammatory response and organ damage. Furthermore, apoptotic cells can even actively suppress inflammation and modulate immune responses by inhibiting the release of proinflammatory cytokines but augmenting the secretion of anti-inflammatory and immunomodulatory cytokines from monocytes/macrophages (MoMa) and dendritic cells. The anti-inflammatory effect of apoptotic cells is mediated by the thrombospondin receptor (CD36) on MoMa and, most likely, other surface receptors, which are not yet molecularly identified. Elevation of intracellular cAMP levels seems to be critically involved in the induction of the anti-inflammatory state in MoMa. \u0000 \u0000 \u0000 \u0000These findings have important implications for clinical medicine. On the one hand side, exposure to high amounts of apoptotic cells in conditions such as cancer or certain viral infections may result in clinically relevant immunosuppression. On the other hand side, therapeutic induction of apoptosis can ameliorate inflammatory diseases. Furthermore, pathogens can misuse apoptotic cells as ‘Trojan horses’ to silently infect and paralyze macrophages. We point out that several pathogens such as HIV, Plasmodium falciparum, Trypanosoma cruzi and Leishmania major mimic apoptotic cells for silent entry and immune escape. \u0000 \u0000 \u0000 \u0000Albeit apoptotic cells exert immunosuppressive effects, the impaired clearance of dead cells causes the release of potential autoantigens and, thereby, fosters autoimmunity. At least in a subgroup of patients with systemic lupus erythematosus impaired phagocytosis of dead cells by macrophages has been observed and may contribute to the etiopathogenesis of this autoimmune disorder.","PeriodicalId":88702,"journal":{"name":"Signal transduction","volume":"64 1","pages":"356-365"},"PeriodicalIF":0.0,"publicationDate":"2005-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/SITA.200500071","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50950344","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The cellular hydration state: role in apoptosis and proliferation","authors":"F. Schliess, D. Häussinger","doi":"10.1002/SITA.200400046","DOIUrl":"https://doi.org/10.1002/SITA.200400046","url":null,"abstract":"Small cell volume changes occur within minutes in response to fluctuations of ambient osmolarity but also under the influence of hormones, substrates, second messengers, and oxidative stress. Isoosmotic cell swelling due to retention of inorganic ions and amino acids is obligatory during the cell cycle whereas cell shrinkage as a result of osmolyte release is an early hallmark of apoptosis known as apoptotic volume decrease. Cell volume changes are registered by osmosensing structures which trigger signals involved in the control of metabolism and gene expression. This review considers the hypothesis that cell volume-dependent signals integrate into the overall signal transduction mediating apoptosis and cell cycle progression, respectively. Understanding the role of cell hydration changes in apoptosis and proliferation is of clinical relevance and provides novel therapeutic aspects.","PeriodicalId":88702,"journal":{"name":"Signal transduction","volume":"16 5","pages":"297-302"},"PeriodicalIF":0.0,"publicationDate":"2005-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/SITA.200400046","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50949945","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NFκB: cell survival or cell death?","authors":"E. Strozyk, D. Kulms","doi":"10.1002/SITA.200500070","DOIUrl":"https://doi.org/10.1002/SITA.200500070","url":null,"abstract":"The present review outlines that the different pathways and components that may influence NFκB, to convert it from an inhibitor of apoptosis into a promoter of apoptosis, are quite versatile. As a consequence inhibition of the NFκB as a global concept to fight cancer should be reconsidered, although of course it seems reasonable for many incidences. Conclusively, cancer therapy can not be generalized but requires individual treatment. (An abstract was missing and has been ‘invented’, please correct if needed; no more than 200 words)","PeriodicalId":88702,"journal":{"name":"Signal transduction","volume":"4 1","pages":"334-349"},"PeriodicalIF":0.0,"publicationDate":"2005-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/SITA.200500070","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50950333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of extracellular signal‐regulated protein kinase and phosphatidylinositol 3‐kinase in neuronal cell death and survival","authors":"G. Thiel, I. Bauer, O. G. Rössler","doi":"10.1002/SITA.200500068","DOIUrl":"https://doi.org/10.1002/SITA.200500068","url":null,"abstract":"The survival of neurons requires, at some point, the presence of neurotrophic factors and depends on competition for a limited supply of survival factors. The neurotrophin brain-derived neurotrophic factor (BDNF) is the ligand for the TrkB neurotrophin receptor, the most abundant Trk receptor in the brain. Two key signaling pathways are induced following binding of BDNF to its cognate receptor that are characterized by the activation of extracellular signal-regulated protein kinase (ERK) and phosphatidylinositol 3-kinase (PI3 kinase). Many reports have assigned a cellular survival function to the activation of ERK and/or PI3 kinase, in line with the reported neuroprotective activity of neurotrophin receptor activation. The activation of PI3 kinase by BDNF represents the dominant survival pathway, whereas the ERK signaling pathway has no or only a marginal role. However, a sustained activation of ERK, lasting for several hours, protects neurons from growth factor deprivation-induced cell death, indicating that the duration of ERK activation is of major importance for its neuroprotective biological function. The activation of ERK and PI3 kinase does not provide protection against oxidative glutamate toxicity. Thus, the biochemical events underlying neuronal cell death induction by the lack of trophic support or via oxidative stress are distinct.","PeriodicalId":88702,"journal":{"name":"Signal transduction","volume":"39 9","pages":"322-333"},"PeriodicalIF":0.0,"publicationDate":"2005-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/SITA.200500068","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50950651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modulating T cell signaling cascades by HMG-CoA reductase inhibitors","authors":"S. Waiczies, T. Prozorovski, F. Zipp","doi":"10.1002/SITA.200500058","DOIUrl":"https://doi.org/10.1002/SITA.200500058","url":null,"abstract":"The modulation of undesirable immune responses is a novel and exciting property of statins. These drugs were initially designed to lower lipid levels by specifically inhibiting the rate-limiting enzyme HMGCR (3-hydroxy-3- methylglutaryl (HMG)-CoA reductase; EC 1.1.1.88; standard protein abbreviation HMG-CoA reductase), which is important for cholesterol synthesis. Various mechanisms accounting for the anti-inflammatory properties of statins have been proposed: preliminary studies reported an interference in MHC class II presentation necessary for transmitting antigen-specific signals to T cells but subsequently a direct impact on various intracellular T cell molecules independent of antigen presentation or T cell receptor triggering was also reported. Several groups including ours have recently reported the benefits of treating various animal models of T cell-mediated autoimmune disorders such as multiple sclerosis and rheumatoid arthritis with HMGCR inhibitors. Although a plethora of molecular processes have been reported, the main biological alterations responsible for modulating T cell response by statins involve (I) a direct interference in T cell cycle progression and induction of anergy and (II) a shift in the differentiation status of T-helper (Th) effector cells towards a regulatory phenotype. The impact of statins on the T cellular immune response is discussed here in detail.","PeriodicalId":88702,"journal":{"name":"Signal transduction","volume":"30 2","pages":"231-244"},"PeriodicalIF":0.0,"publicationDate":"2005-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/SITA.200500058","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50950402","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial: Immune surveillance of the brain and multiple sclerosis","authors":"O. Ullrich","doi":"10.1002/SITA.200590008","DOIUrl":"https://doi.org/10.1002/SITA.200590008","url":null,"abstract":"","PeriodicalId":88702,"journal":{"name":"Signal transduction","volume":"1 1","pages":"229-230"},"PeriodicalIF":0.0,"publicationDate":"2005-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/SITA.200590008","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50950675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular mechanisms of neuronal apoptosis in chronic inflammatory CNS diseases","authors":"R. Diem, Muriel B. Sättler, K. Maier, M. Bähr","doi":"10.1002/SITA.200500065","DOIUrl":"https://doi.org/10.1002/SITA.200500065","url":null,"abstract":"In the adult CNS, apoptosis of neuronal populations contributes to manifestation of clinical symptoms during several neurodegenerative disorders. In multiple sclerosis (MS), an inflammatory demyelinating CNS disease, neurodegeneration has long been thought to occur secondary and late during clinical course. However, in the last years, post-mortem studies of human brain tissue as well as data from animal models have shown that apoptosis of neurons reaches a significant extent already in the early stages of the disease. As neurodegeneration in MS correlates with permanent neurological deficits in patients, understanding the mechanisms would be an important pre-condition for designing appropriate neuroprotective therapies. This review article gives an overview about current data concerning features and molecular mechanisms of neuronal apoptosis in chronic inflammatory autoimmune CNS diseases. Furthermore, possible implications for the development of neuroprotective therapies are discussed.","PeriodicalId":88702,"journal":{"name":"Signal transduction","volume":"71 1","pages":"250-257"},"PeriodicalIF":0.0,"publicationDate":"2005-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/SITA.200500065","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50950589","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of dipeptidyl peptidase IV (DP IV, CD26) in T cell activation and multiple sclerosis","authors":"D. Reinhold, T. Kähne, A. Steinbrecher, A. Gerber, V. Preller, Bettina Gornickel, S. Wrenger, S. Ansorge, S. Brocke","doi":"10.1002/SITA.200500069","DOIUrl":"https://doi.org/10.1002/SITA.200500069","url":null,"abstract":"The ectoenzyme dipeptidyl peptidase IV (DP IV; E.C. 3.4.14.5; CD26) plays a crucial role in T cell activation, representing a new type of costimulatory T cell structure. Effectors of DP IV-like activity, including naturally occurring and specific synthetic inhibitors, suppress DNA synthesis as well as cytokine production (IL-2, IL-10, IL-12, IFN-γ) of stimulated T cells. These effects are in part caused by the immunosuppressive cytokine TGF-β1, leading to blockade of the cell cycle at the restriction point G1/S via p27kip. At the same time, DP IV inhibitors provoke tyrosine phosphorylation and p38 MAP kinase activation. Elevated numbers of CD26+ T cells were observed in patients with autoimmune diseases such as rheumatoid arthritis or multiple sclerosis (MS). The expression of DP IV/CD26 in resting T cell clones derived from patients with MS was found to be 3- to 4-fold higher than on resting peripheral blood T cells from healthy persons. In myelin-specific T cells from MS patients, DP IV inhibitors suppress DNA synthesis, as well as IFN-γ, IL-4 and TNF-α production. Moreover, in experimental autoimmune encephalomyelitis (EAE), a well characterized CD4+ T cell-mediated autoimmune disease leading to CNS inflammation and demyelinization, administration of a DP IV/CD26 inhibitor prevents clinical and neuropathological signs of EAE and suppresses ongoing disease. This review summarizes evidence for the role of DP IV enzyme activity in regulation of T cell activation, outlines signal transduction mechanisms used or affected by this enzyme and provides support for the concept of a novel peptidase-based immunosuppressive approach to treat autoimmune diseases like MS.","PeriodicalId":88702,"journal":{"name":"Signal transduction","volume":"5 1","pages":"258-265"},"PeriodicalIF":0.0,"publicationDate":"2005-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/SITA.200500069","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50950724","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New aspects regarding mechanisms of tissue damage in the course of autoimmune demyelination","authors":"O. Aktas","doi":"10.1002/SITA.200500059","DOIUrl":"https://doi.org/10.1002/SITA.200500059","url":null,"abstract":"Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system (CNS) and the major cause of neurological disability in young adults in Western countries. Over the last decades, it has become evident that the immune system specifically attacks the myelin sheath within the CNS and induces recurrent or persisting neurological deficits in patients. This review focuses on selected new aspects of the underlying mechanisms linking autoimmune demyelination and irreversible brain tissue damage in the course of MS and its animal model, experimental autoimmune encephalomyelitis.","PeriodicalId":88702,"journal":{"name":"Signal transduction","volume":"64 1","pages":"245-249"},"PeriodicalIF":0.0,"publicationDate":"2005-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/SITA.200500059","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50950452","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}