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1.
Ludivine A. Pradelli Marie Bénéteau Jean-Ehrland Ricci 《Cellular and molecular life sciences : CMLS》2010,67(10):1589-1597
Mitochondria control whether a cell lives or dies. The role mitochondria play in deciding the fate of a cell was first identified
in the mid-1990s, because mitochondria-enriched fractions were found to be necessary for activation of death proteases, the
caspases, in a cell-free model of apoptotic cell death. Mitochondrial involvement in apoptosis was subsequently shown to be
regulated by Bcl-2, a protein that was known to contribute to cancer in specific circumstances. The important role of mitochondria
in promoting caspase activation has therefore been a major focus of apoptosis research; however, it is also clear that mitochondria
contribute to cell death by caspase-independent mechanisms. In this review, we will highlight recent findings and discuss
the mechanism underlying the mitochondrial control of apoptosis and caspase-independent cell death. 相似文献
2.
Cbl proteins control multiple cellular processes by acting as ubiquitin ligases and multifunctional adaptor molecules. They are involved in the control of cell proliferation, differentiation and cell morphology, as well as in pathologies such as autoimmune diseases, inflammation and cancer. Here we review recent advances in understanding the role of Cbl and the importance of a growing repertoire of Cbl-interacting proteins in the regulation of signaling pathways triggered by growth factors, antigens, cell adhesion, cytokines and hormones. We also address key issues of the nature of proteins that bind Cbl in particular cells, where they are located, and how they are altered or traffic within cells upon stimulation. It is becoming obvious that temporal and spatial changes in Cbl signaling networks are essential for the control of physiological processes in a variety of cells and organs and that their deregulation can result in the development of human diseases.Received 22 January 2003; received after revision 11 March 2003; accepted 26 March 2003 相似文献
3.
Sara Proietti Alessandra Cucina Mirko Minini Mariano Bizzarri 《Cellular and molecular life sciences : CMLS》2017,74(21):4015-4025
The long-recognized fact that oxidative stress within mitochondria is a hallmark of mitochondrial dysfunction has stimulated the development of mitochondria-targeted antioxidant therapies. Melatonin should be included among the pharmacological agents able to modulate mitochondrial functions in cancer, given that a number of relevant melatonin-dependent effects are triggered by targeting mitochondrial functions. Indeed, melatonin may modulate the mitochondrial respiratory chain, thus antagonizing the cancer highly glycolytic bioenergetic pathway of cancer cells. Modulation of the mitochondrial respiratory chain, together with Ca2+ release and mitochondrial apoptotic effectors, may enhance the spontaneous or drug-induced apoptotic processes. Given that melatonin may efficiently counteract the Warburg effect while stimulating mitochondrial differentiation and mitochondrial-based apoptosis, it is argued that the pineal neurohormone could represent a promising new perspective in cancer treatment strategy. 相似文献
4.
Apoptosis regulation in the mammary gland 总被引:14,自引:0,他引:14
Epithelial apoptosis has a key role in the development and function of the mammary gland. It is involved with
the formation of ducts during puberty and is required to remove excess epithelial cells after lactation so that
the gland can be prepared for future pregnancies. Deregulated apoptosis contributes to malignant progression in
the genesis of breast cancer. Since epithelial cell apoptosis in the lactating mammary gland can be synchronised
by forced weaning, it has been possible to undertake biochemical analysis of the pathways involved. Together with
the targeted overexpression or deletion of candidate genes, these approaches have provided a unique insight into
the complex mechanisms of apoptosis regulation in vivo. This review explores what is currently known about the
triggers for apoptosis in the normal mammary gland, and how they link with the intrinsic apoptotic machinery.Received 23 September 2003; received after revision 13 February 2004; accepted 3 March 2004 相似文献
5.
6.
Programmed cell clearance 总被引:10,自引:0,他引:10
Fadeel B 《Cellular and molecular life sciences : CMLS》2003,60(12):2575-2585
Apoptosis, a physiological process of self-annihilation, is essential during development and for the maintenance of tissue homeostasis. Considerable efforts have been made in recent years to elucidate the molecular mechanisms that govern this mode of cellular demise; however, the subsequent recognition and removal of apoptotic corpses by neighboring phagocytes has received less attention. Nevertheless, macrophage engulfment of apoptotic cells is known to be important in the remodeling of tissues, and contributes to the resolution of inflammation through the removal of effete cells prior to the release of noxious cellular constituents. Moreover, apoptotic cells are a potential source of self-antigens, and clearance of cell corpses is thought to preclude the induction of autoimmune responses. The view is thus emerging that tissue homeostasis is dependent not only on the balance between mitosis and apoptosis, but also on the rate of apoptosis versus that of cell clearance. This review aims to discuss the mechanisms and consequences of macrophage recognition and disposal of apoptotic cells, a process which will be referred to as programmed cell clearance.Received 16 April 2003; received after revision 22 May 2003; accepted 26 May 2003 相似文献
7.
Nitric oxide can inhibit apoptosis or switch it into necrosis 总被引:4,自引:0,他引:4
Melino G Catani MV Corazzari M Guerrieri P Bernassola F 《Cellular and molecular life sciences : CMLS》2000,57(4):612-622
Nitric oxide (NO) and its related molecules are important messengers that play central roles in pathophysiology. Redox modulation of thiol groups on protein cysteine residues by S-nitrosylation can modulate protein function. NO has emerged as a potent regulator of apoptosis in many cell types, either preventing cell death or driving an apoptotic response into a necrotic one. NO protects neuroblastoma cells from retinoid- and cisplatin-induced apoptosis, without significantly increasing necrotic cell damage. Nitrosylation of thiol groups of several critical factors may be important for cell survival. Indeed, S-nitrosylation of the active-site cysteine residue of apoptotic molecules, such as caspases and tissue transglutaminase, results in the inhibition of their catalytic activities and has important implications for the regulation of apoptosis by NO. On the other hand, NO is able to shift the anti-CD95- and ceramide-triggered apoptotic response of Jurkat T cells into necrotic cell death. In these apoptotic models, NO is therefore unable to solely inhibit cell death, indicating that it may act below the point of no return elicited by CD95-ligation and ceramide stimulation. 相似文献
8.
Expression of membrane and nuclear melatonin receptor mRNA and protein in the mouse immune system 总被引:3,自引:0,他引:3
Carrillo-Vico A García-Pergañeda A Naji L Calvo JR Romero MP Guerrero JM 《Cellular and molecular life sciences : CMLS》2003,60(10):2272-2278
The neurohormone melatonin plays a fundamental role in neuroimmunomodulation of several mammalian species, including mice. This effect is supported by the existence of specific melatonin-binding sites in murine immunocompetent organs. Moreover, using melatonin receptor analogues, several effects of the neurohormone on mice physiology through its membrane and nuclear receptors have been described. The expression of these receptors has never been studied, despite indirect evidence showing the presence of melatonin receptor in the murine immune system. At present, the MT1 and MT2 membrane receptors, and nuclear receptors belonging to the RZR/ROR family have been related to the immunomodulator effect of melatonin. Here, we show the presence of membrane and nuclear melatonin-binding sites in mouse thymus and spleen, using the specific melatonin membrane (S 20098) and nuclear (CGP 52608) receptor agonist. To confirm the presence of melatonin receptors, we analyzed the presence of membrane and nuclear receptor mRNA and protein by RT-PCR, Southern blot, and Western blot. Thus, we show that MT1 and ROR receptor mRNA and protein are expressed in both thymus and spleen, while MT2 receptor mRNA is only detected in the thymus. This expression of melatonin receptors strongly supports the idea of an immunomodulatory role of melatonin through its receptors.Received 2 June 2003; received after revision 6 August 2003; accepted 14 August 2003 相似文献
9.
Gabriela Brumatti Marika Salmanidis Paul G. Ekert 《Cellular and molecular life sciences : CMLS》2010,67(10):1619-1630
Cytokines and growth factors play a crucial role in the maintenance of haematopoietic homeostasis. They transduce signals
that regulate the competing commitments of haematopoietic stem cells, quiescence or proliferation, retention of stem cell
pluripotency or differentiation, and survival or demise. When the balance between these commitments and the requirements of
the organisms is disturbed, particularly when it favours survival and proliferation, cancer may result. Cell death provoked
by loss of growth factor signalling is regulated by the Bcl-2 family of apoptosis regulators, and thus survival messages transduced
by growth factors must regulate the activity of these proteins. Many aspects of direct interactions between cytokine signalling
and regulation of apoptosis remain elusive. In this review, we explore the mechanisms by which cytokines, in particular Interleukin-3
and granulocyte–macrophage colony-stimulating factor, promote cell survival and suppress apoptosis as models of how cytokine
signalling and apoptotic pathways intersect. 相似文献
10.
Menadione-induced apoptosis and the degradation of lamin-like proteins in tobacco protoplasts 总被引:1,自引:0,他引:1
Y.-L. Sun H.-Z. Zhu J. Zhou Y.-R. Dai Z.-H. Zhai 《Cellular and molecular life sciences : CMLS》1999,55(2):310-316
Detection of stereotypic hallmarks of apoptosis during cell death induced by menadione, including DNA laddering and the formation
of apoptotic bodies, is reported. Comet assay and the TdT-mediated dUTP nick end labelling (TUNEL) procedure were also performed
to detect DNA fragmentation. Inhibition of DNA fragmentation by Ac-Asp-Glu-Val-Asp-aldehyde (Ac-DEVD-CHO) and phenylmethylsulfosyl
(PMSF) implicated the involvement of caspase-like proteases in menadione-induced apoptosis in plants. We further studied the
cleavage of lamin-like proteins during apoptosis in menadione-treated tobacco protoplasts. In animals, it has been reported
that the solubilization of nuclear lamina and lamin degradation occurs during apoptotic cell death. However, little is known
about the fate of lamins in apoptotic plant cells. Our study provided evidence that lamin-like proteins degraded into 35-kDa
fragments in tobacco protoplasts induced by menadione, and this preceded DNA fragmentation. The results thus indicated that
proteolytic cleavage of nuclear lamins was also conserved in programmed cell death in plants.
Received 16 November 1998; received after revision 21 December 1998; accepted 23 December 1998 相似文献
11.
B. Zhivotovsky D. H. Burgess S. Orrenius 《Cellular and molecular life sciences : CMLS》1996,52(10-11):968-978
The interleukin-1 β-converting enzyme (ICE)-like family proteases have recently been identified as key enzymes in apoptotic cell death. Among these proteases one can identify specific activities which may be involved in cytokine production or in resident protein cleavage. Several factors influence the constitutive apoptotic mechanism and may provide insight into the role of protease(s) in apoptosis. Although it appears that ICE family members play a most important role in promoting apoptotic cell death, evidence has been advanced that other proteases are also involved in sequential or parallel steps of apoptosis. Activation of a particular protease can lead to processing molecules either of the same or different proteases, leading to an activation of a protease cascade. Here we attempt to summarize the current thinking concerning these proteases and their involvement in apoptosis. 相似文献
12.
Selenocystine (SeC), a naturally occurring selenoamino acid, has been shown to be a novel compound with broad-spectrum anticancer activity. In this study, we showed that SeC triggered time- and dose-dependent apoptosis in A375 human melanoma cells by activating the mitochondria-mediated and death receptor-mediated apoptosis pathways. Pretreatment of cells with a general caspase inhibitor z-VAD-fmk significantly prevented SeC-induced apoptosis. A375 cells exposed to SeC showed an increase in levels of total p53 and phosphorylated p53 (serine-15). Silencing of p53 expression with RNA interference significantly suppressed SeC-induced p53 phosphorylation, caspase activation and apoptotic cell death. Moreover, generation of reactive oxygen species and subsequent induction of DNA strand breaks were found to be upstream mediators of p53 activation induced by SeC. In a nude mice xenograft experiment, SeC significantly inhibited the tumor growth of A375 cells via induction of apoptosis. Taken together, these results suggest the potential applications of SeC in cancer chemoprevention. 相似文献
13.
BH3-only proteins in tumorigenesis and malignant melanoma 总被引:2,自引:0,他引:2
BH3-only proteins are a subset of the Bcl-2 family of apoptotic regulators. BH3-only proteins function as ‘damage sensors’
in the cell; they are activated in response to cellular stress or DNA damage, whereupon they initiate apoptosis. Apoptosis
is the primary mechanism by which the body rids itself of genetically defective cells and is critical for preventing the accumulation
of cells with tumorigenic potential. Therefore, dysregulation of BH3-only proteins may promote tumorigenesis. Furthermore,
functional apoptosis pathways are required for the success of most cancer treatments, including chemotherapy. Resistance to
chemotherapy, as seen with malignant melanoma, often reflects an inability of tumor cells to undergo apoptosis. By deciphering
the roles of BH3-only proteins in tumorigenesis, we may learn how to manipulate cell death pathways to overcome apoptotic
resistance. This review summarizes the current knowledge of BH3-only proteins and how they contribute to tumorigenesis, with
particular attention given to studies involving melanoma.
Received: 12 August 2006; received after revision: 2 October 2006; accepted 13 November 2006 相似文献
14.
Kenis H Hofstra L Reutelingsperger CP 《Cellular and molecular life sciences : CMLS》2007,64(22):2859-2862
The surge in apoptosis research and the discovery of the phosphatidylserine binding properties of annexin A5 have propelled
a tremendous interest in cell death detection technologies. In the past years, annexin A5 has evolved from an efficient assay
for detection of apoptotic cells in vitro to an in vivo molecular imaging technology with potential clinical use. A second key discovery, the specific internalization properties
of annexin A5, has opened the opportunity to use annexin A5 for therapeutic applications. Annexin A5-mediated internalization
creates a novel therapeutic platform for targeted drug delivery and cell entry to treat various diseases, including cancer
and cardiovascular disease.
Received 29 June 2007; received after revision 19 July 2007; accepted 15 August 2007 相似文献
15.
The modular nature of apoptotic signaling proteins 总被引:9,自引:0,他引:9
K. Hofmann 《Cellular and molecular life sciences : CMLS》1999,55(8-9):1113-1128
Apoptosis, initiated by a variety of stimuli, is a physiological process that engages a well-ordered signaling cascade, eventually
leading to the controlled death of the cell. The most extensively studied apoptotic stimulus is the binding of death receptors
related to CD95 (Fas/Apo1) by their respective ligands. During the last years, a considerable number of proteins have been
identified which act together in the receptor-proximal part of the signaling pathway. Based on localized regions of sequence
similarity, it has been predicted that these proteins consist of several independently folding domains. In several cases these
predictions have been confirmed by structural studies; in other cases they are at least supported by experimental data. This
review focuses on the three most widespread domain families found in the apoptotic signaling proteins: the death domain, the
death effector domain and the caspase recruitment domain. The recently discovered analogies between these domains, both in
structure and in function, have shed some light on the overall architecture of the pathway leading from death receptor ligation
to the activation of caspases and eventually to the apoptotic phenotype.
Received 8 October 1998; received after revision 8 January 1999; accepted 8 January 1999 相似文献
16.
The maintenance of mucosal barrier equilibrium in the intestine requires a delicate and dynamic balance between enterocyte
loss by apoptosis and the generation of new cells by proliferation from stem cell precursors at the base of the intestinal
crypts. When the balance shifts towards either excessive or insufficient apoptosis, a broad range of gastrointestinal diseases
can manifest. Recent work from a variety of laboratories has provided evidence in support of a role for receptors of the innate
immune system, including Toll-like receptors 2, 4, and 9 as well as the intracellular pathogen recognition receptor NOD2/CARD15,
in the initiation of enterocyte apoptosis. The subsequent induction of enterocyte apoptosis in response to the activation
of these innate immune receptors plays a key role in the development of various intestinal diseases, including necrotizing
enterocolitis, Crohn’s disease, ulcerative colitis, and intestinal cancer. This review will detail the regulatory pathways
that govern enterocyte apoptosis, and will explore the role of the innate immune system in the induction of enterocyte apoptosis
in gastrointestinal disease. 相似文献
17.
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
18.
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
19.
Sreerupa Challa Francis Ka-Ming Chan 《Cellular and molecular life sciences : CMLS》2010,67(19):3241-3253
Recent evidence indicates that cell death can be induced through multiple mechanisms. Strikingly, the same death signal can
often induce apoptotic as well as non-apoptotic cell death. For instance, inhibition of caspases often converts an apoptotic
stimulus to one that causes necrosis. Because a dedicated molecular circuitry distinct from that controlling apoptosis is
required for necrotic cell injury, terms such as “programmed necrosis” or “necroptosis” have been used to distinguish stimulus-dependent
necrosis from those induced by non-specific traumas (e.g., heat shock) or secondary necrosis induced as a consequence of apoptosis.
In several experimental models, programmed necrosis/necroptosis has been shown to be a crucial control point for pathogen-
or injury-induced inflammation. In this review, we will discuss the molecular mechanisms that regulate programmed necrosis/necroptosis
and its biological significance in pathogen infections, drug-induced cell injury, and trauma-induced tissue damage. 相似文献
20.
Neuroreplacement therapy and stem cell biology under disease conditions 总被引:22,自引:0,他引:22
Sugaya K 《Cellular and molecular life sciences : CMLS》2003,60(9):1891-1902
Recent advances in stem cell technology are expanding our ability to replace a variety of cells throughout the body. In the past, neurological diseases caused by the degeneration of neuronal cells were considered incurable because of a long-held 'truism'; neurons do not regenerate during adulthood. However, this statement has been challenged, and we have now found much evidence that the brain is indeed capable of regenerating neurons after maturing. Based on this new concept, researchers have shown neural differentiation of stem cells and recovery of function following transplantation of these cells into the brain. These results may promise a bright future for clinical applications of stem cell strategies in neurological diseases; however, we must consider the pathophysiological environments of individual diseases that may affect stem cell biology. Before we begin to develop clinical applications, we must consider environmental factors that have not been discussed in the current preclinical studies. Here, we study cases of Alzheimer's disease and schizophrenia and discuss the effects of environmental factors under disease conditions.Received 15 January 2003; received after revision 7 April 2003; accepted 8 April 2003 相似文献