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1.
Ferioli ME Bottone MG Soldani C Pellicciari C 《Cellular and molecular life sciences : CMLS》2004,61(21):2767-2773
The suggestion has been made that polyamines may be involved in the control of cell death, since exceedingly high or low levels induce apoptosis in different cell systems. For a deeper insight into the relationship between apoptosis and polyamine metabolism, we investigated in vitro the effect on rat thymocytes of mitoguazone (MGBG, which inhibits S-adenosylmethionine decarboxylase, i.e. a key enzyme in the polyamine biosynthetic pathway). Thymocytes were selected as an especially suitable model system, since they undergo spontaneous apoptosis in vivo and can be easily induced to apoptose in vitro by etoposide, used here as an apoptogenic agent. MGBG protected thymocytes from both spontaneous and drug-induced apoptosis, and this protective effect was associated with a decrease in polyamine oxidase activity and total polyamine levels.Received 7 July 2004; received after revision 2 September 2004; accepted 9 September 2004 相似文献
2.
Chaim Kahana 《Cellular and molecular life sciences : CMLS》2009,66(15):2479-2488
The polyamines are small basic molecules essential for cellular proliferation and viability. An autoregulatory circuit that
responds to the intracellular level of polyamines regulates their production. In the center of this circuit is a family of
small proteins termed antizymes. Antizymes are themselves regulated at the translational level by the level of polyamines.
Antizymes bind ornithine decarboxylase (ODC) subunits and target them to ubiquitin-independent degradation by the 26S proteasome.
In addition, antizymes inhibit polyamine transport across the plasma membrane via an as yet unresolved mechanism. Antizymes
may also interact with and target degradation of other growth-regulating proteins. An inactive ODC-related protein termed
antizyme inhibitor regulates polyamine metabolism by negating antizyme functions. The ability of antizymes to degrade ODC,
inhibit polyamine uptake and consequently suppress cellular proliferation suggests that they act as tumor suppressors, while
the ability of antizyme inhibitors to negate antizyme function indicates their growth-promoting and oncogenic potential. 相似文献
3.
L. Fesus A. Madi Z. Balajthy Z. Nemes Z. Szondy 《Cellular and molecular life sciences : CMLS》1996,52(10-11):942-949
Clarification of the molecular details of forms of natural cell death, including apoptosis, has become one of the most challenging issues of contemporary biomedical sciences. One of the effector elements of various cell death pathways is the covalent cross-linking of cellular proteins by transglutaminases. This review will discuss the accumulating data related to the induction and regulation of these enzymes, particularly of tissue type transglutaminase, in the molecular program of cell death. A wide range of signalling pathways can lead to the parallel induction of apoptosis and transglutaminase, providing a handle for better understanding the exact molecular interactions responsible for the mechanism of regulated cell death. 相似文献
4.
Polyamines are small charged molecules essential for various cellular functions, but at high levels they are cytotoxic. Two
yeast kinases, SKY1 and PTK2, have been demonstrated to regulate polyamine tolerance. Here we report the identification and
characterization of additional genes involved in regulating polyamine tolerance: YGL007W, FES1 and AGP2. Deletion of YGL007W,
an open reading frame located within the promoter of the membrane proton pump PMA1, decreased Pma1p expression. Deletion of
FES1 or AGP2 resulted in reduced polyamine uptake. While high-affinity spermine uptake was practically absent in agp2Δ cells, fes1Δ cells displayed only reduced affinity towards spermine. Despite the reduced uptake, the resistant strains accumulated significant
levels of polyamines and displayed increased ornithine decarboxylase activity, suggesting reduced polyamine sensing. Interestingly,
fes1Δ cells were highly sensitive to salt ions, suggesting different underlying mechanisms. These results indicate that mechanisms
leading to polyamine tolerance are complex, and involve components other than uptake.
Received 31 July 2005; received after revision 7 October 2005; accepted 19 October 2005 相似文献
5.
Maldonado-Celisa ME Roussia S Foltzer-Jourdainne C Gossé F Lobstein A Habold C Roessner A Schneider-Stock R Raul F 《Cellular and molecular life sciences : CMLS》2008,65(9):1425-1434
We showed previously that inhibition of polyamine catabolism with the polyamine oxidase inhibitor MDL 72527 (MDL) potentiates
the apoptotic effects of apple procyanidins (Pcy) in SW620 cells. Here we report that Pcy caused an activation of the intrinsic
apoptotic pathway through enhanced polyamine catabolism and mitochondrial membrane depolarization. MDL in the presence of
Pcy caused a profound intracellular depletion of polyamines and exerted a protective effect on mitochondrial functions. MDL
potentiation of Pcy-triggered apoptosis was reversed by addition of exogenous polyamines. In addition, MDL in combination
with Pcy activated the extrinsic apoptotic pathway through enhanced TRAIL-death receptor (DR4/DR5) expression. Potentiation
of Pcy-triggered apoptosis by MDL was inhibited when cells were exposed to specific inhibitors of DR4/DR5. These data indicate
that the depletion of intracellular polyamines by MDL in the presence of Pcy caused a switch from intrinsic to extrinsic apoptotic
pathways in human colon cancer-derived metastatic cells.
Received 15 January 2008; received after revision 19 February 2008; accepted 7 March 2008 相似文献
6.
Increasing evidence links blood coagulation proteins with the regulation of acute and chronic inflammatory disease. Of particular
interest are vitamin K-dependent proteases, which are generated as a hemostatic response to vascular injury, but can also
initiate signal transduction via interactions with vascular receptors. The endothelial cell protein C receptor (EPCR) is a
multi-ligand vitamin K-dependent protein receptor for zymogen and activated forms of plasma protein C and factor VII. Although
the physiological role of the EPCR-FVII(a) interaction is not well-understood, protein C binding to EPCR facilitates rapid
generation of APC in response to excessive thrombin generation, and is a central requirement for the multiple signal-transduction
cascades initiated by APC on both vascular endothelial and innate immune cells. Exciting recent studies have highlighted the
emerging role of EPCR in modulating the cytoprotective properties of APC in a number of diverse inflammatory disorders. In
this review, we describe the structure–function relationships, signal transduction pathways, and cellular interactions that
enable EPCR to modulate the anticoagulant and anti-inflammatory properties of its vitamin K-dependent protein ligands, and
examine the relevance of EPCR to both thrombotic and inflammation-associated disease. 相似文献
7.
Suresh Ramakrishna Bharathi Suresh Kwang-Hyun Baek 《Cellular and molecular life sciences : CMLS》2011,68(1):15-26
It has become apparent that ubiquitination plays a critical role in cell survival and cell death. In addition, deubiquitinating
enzymes (DUBs) have been determined to be highly important regulators of these processes. Cells can be subjected to various
stresses and respond in a variety of different ways ranging from activation of survival pathways to the promotion of cell
death, which eventually eliminates damaged cells. The regulatory mechanisms of apoptosis depend on the balanced action between
ubiquitination and deubiquitination systems. There is a growing recognition that DUBs play essential roles in regulating several
binding partners to modulate the process of apoptosis. Thus, the interplay between the timing of DUB activity and the specificity
of ubiquitin attachment and removal from its substrates during apoptosis is important to ensure cellular homeostasis. This
review discusses the role of a few ubiquitin-specific DUBs that are involved in either promoting or suppressing the process
of apoptosis. 相似文献
8.
The polyamine putrescine might be formed via a degradation (catalyzed by spermidine/spermine N1-acetyltransferase, SSAT) of the higher polyamines spermidine and spermine to putrescine. The involvement of different intracellular signal pathways in the regulation of putrescine formation was studied in explants and in cultured cells of rat parotid glands by using receptor agonists that activate separate second messenger systems, and measuring their effects on the concentrations of putrescine, spermidine and spermine and on the SSAT activity. The -adrenoceptor agonist isoprenaline, which is an activator of cAMP formation, increased the putrescine concentration and stimulated the SSAT activity. Pilocarpine, a drug that activates the muscarinic receptors and thereby enhances the phosphoinositide turnover, had no effect on either the polyamine concentrations or on the SSAT activity. Epidermal growth factor (EGF), which induces activation of a protein tyrosine kinase, had no effect on the polyamine concentrations or on the SSAT activity. The adenylate cyclase activator forskolin increased the glandular levels of putrescine. Taken together, these findings suggest that increases in putrescine concentration in cultured rat parotid gland cells are accompanied by accumulation of cAMP. 相似文献
9.
Polyamine-dependent gene expression 总被引:15,自引:0,他引:15
The polyamines spermidine and spermine along with the diamine putrescine are involved in
many cellular processes, including chromatin condensation, maintenance of DNA structure, RNA
processing, translation and protein activation. The polyamines influence the
formation of compacted chromatin and have a well-established role in DNA aggregation. Polyamines
are used in the posttranslational modification of eukaryotic initiation factor 5A, which regulates
the transport and processing of specific RNA. The polyamines also participate in a
novel RNA-decoding mechanism, a translational frameshift, of at least two known genes, the TY1
transposon and mammalian antizyme. Polyamines are crucial for their own regulation and are involved
in feedback mechanisms affecting both polyamine synthesis and catabolism. Recently, it has become
apparent that the polyamines are able to influence the action of the protein kinase
casein kinase 2. Here we address several roles of polyamines in gene expression.Received 27 November 2002; received after revision 9 January 2003; accepted 31 January 2003 相似文献
10.
Regulation of neutrophil apoptosis via death receptors 总被引:4,自引:0,他引:4
11.
Franky Van Herreweghe Nele Festjens Wim Declercq Peter Vandenabeele 《Cellular and molecular life sciences : CMLS》2010,67(10):1567-1579
In this review, we discuss the signal-transduction pathways of three major cellular responses induced by tumor necrosis factor
(TNF): cell survival through NF-κB activation, apoptosis, and necrosis. Recruitment and activation of caspases plays a crucial
role in the initiation and execution of TNF-induced apoptosis. However, experimental inhibition of caspases reveals an alternative
cell death pathway, namely necrosis, also called necroptosis, suggesting that caspases actively suppress the latter outcome.
TNF-induced necrotic cell death crucially depends on the kinase activity of receptor interacting protein serine-threonine
kinase 1 (RIP1) and RIP3. It was recently demonstrated that ubiquitination of RIP1 determines whether it will function as
a pro-survival or pro-cell death molecule. Deeper insight into the mechanisms that control the molecular switches between
cell survival and cell death will help us to understand why TNF can exert so many different biological functions in the etiology
and pathogenesis of human diseases. 相似文献
12.
13.
Arabinogalactan-proteins: structure, expression and function 总被引:26,自引:0,他引:26
A.M. Showalter 《Cellular and molecular life sciences : CMLS》2001,58(10):1399-1417
Arabinogalactan-proteins (AGPs) are a family of extensively glycosylated hydroxyproline-rich glycoproteins that are thought to have important roles in various aspects of plant growth and development. After a brief introduction to AGPs highlighting the problems associated with defining and classifying this diverse family of glycoproteins, AGP structure is described in terms of the protein component (including data from molecular cloning), carbohydrate component, processing of AGPs (including recent data on glycosylphosphatidylinositol membrane anchors) and overall molecular shape. Next, the expression of AGPs is examined at several different levels, from the whole plant to the cellular levels, using a variety of experimental techniques and tools. Finally, AGP function is considered. Although the existing functional evidence is not incontrovertible, it does clearly point to roles for AGPs in vegetative, reproductive, and cellular growth and development as well as programmed cell death and social control. In addition and most likely inextricably linked to their functions, AGPs are presumably involved in molecular interactions and cellular signaling at the cell surface. Some likely scenarios are discussed in this context. AGPs also have functions of real or potential commercial value, most notably as emulsifiers in the food industry and as potential immunological regulators for human health. Several important questions remain to be answered with respect to AGPs. Clearly, elucidating the unequivocal functions of particular AGPs and relating these functions to their respective structures and modes of action remain as major challenges in the years ahead. 相似文献
14.
Bommhardt U Beyer M Hünig T Reichardt HM 《Cellular and molecular life sciences : CMLS》2004,61(3):263-280
The thymus is central to the establishment of a functioning immune system. Here is the place where T cells mature from hematopoietic progenitors, driven by mutual interactions of stromal cells and the developing thymocytes. As a result, different types of T cells are generated, all of which have been carefully selected for the ability to act in host defense towards non-self and against the potential to mount pathogenic self-reactive autoimmune responses. In this review we summarize our present knowlege on the lineage decisions taking place during this development, the selection processes responsible for shaping the T cell antigen-receptor repertoire, the interactions with the stromal components and the signal transduction pathways which transform the interactions with the thymic microenvironment into cellular responses of survival, proliferation, differentiation and, importantly, also of cell death.
Received 12 June 2003; received after revision 22 July 2003; accepted 28 July 2003 相似文献
15.
Tetraspanins regulate a variety of cellular functions. However, the general cellular mechanisms by which tetraspanins regulate these functions remain poorly understood. In this article we collected the observations that tetraspanins regulate the formation and/or development of various tubular structures of cell membrane. Because tetraspanins and their associated proteins (1) are localized at the tubular structures, such as the microvilli, adhesion zipper, foot processes, and penetration peg, and/or (2) regulate the morphogenesis of these membrane tubular structures, tetraspanins probably modulate various cellular functions through these membrane tubular structures. Some tetraspanins inhibit membrane tubule formation and/or extension, while others promote them. We predict that tetraspanins regulate the formation and/or development of various membrane tubular structures: (1) microvilli or nanovilli at the plasma membranes free of cell and matrix contacts, (2) membrane tubules at the plasma membrane of cell-matrix and cell-cell interfaces, and (3) membrane tubules at the intracellular membrane compartments. These different membrane tubular structures likely share a common morphogenetic mechanism that involves tetraspanins. Tetraspanins probably regulate the morphogenesis of membrane tubular structures by altering (1) the biophysical properties of the cell membrane such as curvature and/or (2) the membrane connections of cytoskeleton. Since membrane tubular structures are associated with cell functions such as adhesion, migration, and intercellular communication, in all of which tetraspanins are involved, the differential effects of tetraspanins on membrane tubular structures likely lead to the functional difference of tetraspanins. 相似文献
16.
Huntington’s disease: from huntingtin function and dysfunction to therapeutic strategies 总被引:3,自引:0,他引:3
Borrell-Pagès M Zala D Humbert S Saudou F 《Cellular and molecular life sciences : CMLS》2006,63(22):2642-2660
Huntington’s disease (HD) is a neurodegenerative disorder that usually starts in middle age and is characterized by involuntary
movements (chorea), personality changes and dementia, leading to death within 10–20 years. The defective gene in HD contains
a trinucleotide CAG repeat expansion within its coding region that expresses a polyglutamine repeat in the protein huntingtin.
Together with the characteristic formation of aggregates in HD, aberrant protein interactions and several post-translational
modifications affect huntingtin during disease progression and lead to the dysfunction and death of selective neurons in the
brains of patients. The exact molecular mechanisms by which mutant huntingtin induces cell death are not completely understood
but may involve the gain of new toxic functions and the loss of the beneficial properties of huntingtin. This review focuses
on the cellular functions in which huntingtin is involved and how a better understanding of pathogenic pathways can lead to
new therapeutic approaches.
Received 24 May 2006; received after revision 5 July 2006; accepted 23 August 2006 相似文献
17.
Arginase expression in peritoneal macrophages and increase in circulating polyamine levels in mice infected with Schistosoma mansoni 总被引:5,自引:0,他引:5
Abdallahi OM Bensalem H Augier R Diagana M De Reggi M Gharib B 《Cellular and molecular life sciences : CMLS》2001,58(9):1350-1357
We investigated the nitric oxide (NO) synthase and arginase pathways in resident peritoneal macrophages of mice infected
with the tropical parasite Schistosoma mansoni. The two enzymes may have opposite effects, insofar as NO may be involved in the killing of the parasite whereas arginase
may stimulate parasite growth via polyamine synthesis. We determined the effects of the infection on the expression and activity
of the two enzymes in macrophages, before and after cytokine activation. Cells from infected mice expressed the hepatic type
I arginase, whereas in control cells, the enzyme was expressed only after cytokine activation, as were NO synthase II and
type II arginase in both groups of cells. Moreover, we found that in infected mice, arginase expression in macrophages was
associated with a ten fold increase in the concentration of circulating ornithine-derived polyamines. This may be of pathological
importance, since parasitic helminths are though to be dependent on their hosts for the uptake and interconversion of polyamines.
Received 13 March 2001; received after revision 4 May 2001; accepted 7 June 2001 相似文献
18.
D. Mekahli Jan B. Parys G. Bultynck L. Missiaen H. De Smedt 《Cellular and molecular life sciences : CMLS》2013,70(15):2697-2712
The cystic phenotype in autosomal dominant polycystic kidney disease is characterized by a profound dysfunction of many cellular signaling patterns, ultimately leading to an increase in both cell proliferation and apoptotic cell death. Disturbance of normal cellular Ca2+ signaling seems to be a primary event and is clearly involved in many pathways that may lead to both types of cellular responses. In this review, we summarize the current knowledge about the molecular and functional interactions between polycystins and multiple components of the cellular Ca2+-signaling machinery. In addition, we discuss the relevant downstream responses of the changed Ca2+ signaling that ultimately lead to increased proliferation and increased apoptosis as observed in many cystic cell types. 相似文献
19.
Machnicka B Grochowalska R Bogusławska DM Sikorski AF Lecomte MC 《Cellular and molecular life sciences : CMLS》2012,69(2):191-201
This review focuses on the recent advances in functions of spectrins in non-erythroid cells. We discuss new data concerning
the commonly known role of the spectrin-based skeleton in control of membrane organization, stability and shape, and tethering
protein mosaics to the cellular motors and to all major filament systems. Particular effort has been undertaken to highlight
recent advances linking spectrin to cell signaling phenomena and its participation in signal transduction pathways in many
cell types. 相似文献
20.
Apoptotic and necrotic cell death induced by death domain receptors 总被引:29,自引:0,他引:29
Denecker G Vercammen D Declercq W Vandenabeele P 《Cellular and molecular life sciences : CMLS》2001,58(3):356-370
Apoptosis and necrosis are two distinct forms of cell death. Caspases are indispensable as initiators and effectors of apoptotic cell death and are involved in many of the morphological and biochemical features of apoptosis. Major changes in mitochondrial membrane integrity and release of proapoptotic factors, such as cytochrome c from the mitochondrial intermembrane space, play an important sensor and amplifying role during apoptotic cell death. In vitro studies of cell death in cell lines have revealed that inhibition of the classical caspase-dependent apoptotic pathway leads in several cases to necrotic cell death. Thus, the same cell death stimulus can result either in apoptotic or necrotic cell death, depending on the availability of activated caspase. Therefore, death domain receptors may initiate an active caspase-independent necrotic signaling pathway. In this review, we describe what is known about the apoptotic and necrotic cell death pathways. Principal elements of necrosis include mitochondrial oxidative phosphorylation, reactive oxygen production, and non-caspase proteolytic cascades depending on serine proteases, calpains, or cathepsins. 相似文献