共查询到20条相似文献,搜索用时 15 毫秒
1.
E. Sick N. Niederhoffer K. Takeda Y. Landry J.-P. Gies 《Cellular and molecular life sciences : CMLS》2009,66(7):1271-1282
Mast cells play pivotal roles in allergic and inflammatory processes via distinct activation pathways. Mucosal and serosal mast cells are activated by the IgE/FcɛRI pathway, while only serosal mast
cells are activated by basic secretagogues. We show that CD47 receptors are expressed on rat peritoneal mast cells. 4N1K,
a peptide agonist of CD47, rapidly caused exocytosis. Such exocytosis required increased intracellular calcium and was inhibited
by pertussis toxin and an antibody against the βγ dimer of a Gi protein. Cooperation with integrins and glycosylphosphatidylinositol-anchored proteins was necessary, since anti-integrin
antibodies and pretreatment with phosphatidylinositol-phospholipase C reduced exocytosis. Depletion of membrane cholesterol
inhibited exocytosis and decreased CD47 in lipid rafts, consistent with a CD47/integrin/Gi protein complex being located in rafts. An anti-CD47 antibody inhibited exocytosis induced by 4N1K and by mastoparan and
spermine, suggesting that basic secretagogues might target CD47. We propose that 4N1K-stimulated mast cell exocytosis involves
a CD47/integrin/Gi protein complex.
Received 8 December 2008; received after revision 12 January 2009; accepted 29 January 2009 相似文献
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Myosin I is a non-filamentous, single-headed, actin-binding motor protein and is present in a wide range of species from yeast to man. The role of these class I myosins have been studied extensively in simple eukaryotes, showing their role in diverse processes such as actin cytoskeleton organization, cell motility, and endocytosis. Recently, studies in metazoans have begun to reveal more specialized functions of myosin I. It will be a major challenge in the future to examine the physiological functions of each class I myosin in different cell types of metazoans. 相似文献
5.
De Zio D Ferraro E D'Amelio M Simoni V Bordi M Soroldoni D Berghella L Meyer BI Cecconi F 《Cellular and molecular life sciences : CMLS》2008,65(11):1780-1790
Fas-associated factor 1 (Faf1) has been described as a Fas-binding pro-apoptotic protein and as a component of the death-inducing signaling complex (DISC) in Fas-mediated apoptosis. Faf1 is able to potentiate Fas-induced apoptosis in several cell lines, although its specific functions are still not clear. Here we show that Faf1 is highly expressed in several areas of the developing telencephalon. Its expression pattern appears to be dynamic at different embryonic stages and to be progressively confined within limited territories. To decipher the specific role of Faf1 in developing brain, we used cDNA over-expression and mRNA down-regulation experiments to modulate Faf1 expression in telencephalic neural precursor cells, and we showed that in neural cell death Faf1 acts as a Fas-independent apoptotic enhancer. Moreover, we found that Faf1 protein level is down-regulated during apoptosis in a caspase- and Apaf1-dependent manner. 相似文献
6.
Bile acids and bile alcohols in the form of their conjugates are amphipathic end products of cholesterol metabolism with multiple physiological functions. The great variety of bile acids and bile alcohols that are present in vertebrates are tabulated. Bile salts have an enterohepatic circulation resulting from efficient vectorial transport of bile salts through the hepatocyte and the ileal enterocyte; such transport leads to the accumulation of a pool of bile salts that cycles between the liver and intestine. Bile salt anions promote lipid absorption, enhance tryptic cleavage of dietary proteins, and have antimicrobial effects. Bile salts are signaling molecules, activating nuclear receptors in the hepatocyte and ileal enterocyte, as well as an increasing number of G-protein coupled receptors. Bile acids are used therapeutically to correct deficiency states, to decrease the cholesterol saturation of bile, or to decrease the cytotoxicity of retained bile acids in cholestatic liver disease. 相似文献
7.
Stem cell therapy in stroke 总被引:2,自引:1,他引:1
Locatelli F Bersano A Ballabio E Lanfranconi S Papadimitriou D Strazzer S Bresolin N Comi GP Corti S 《Cellular and molecular life sciences : CMLS》2009,66(5):757-772
Recent work has focused on cell transplantation as a therapeutic option following ischemic stroke, based on animal studies
showing that cells transplanted to the brain not only survive, but also lead to functional improvement. Neural degeneration
after ischemia is not selective but involves different neuronal populations, as well as glial and endothelial cell types.
In models of stroke, the principal mechanism by which any improvement has been observed, has been attributed to the release
of trophic factors, possibly promoting endogenous repair mechanisms, reducing cell death and stimulating neurogenesis and
angiogenesis. Initial human studies indicate that stem cell therapy may be technically feasible in stroke patients, however,
issues still need to be addressed for use in human subjects.
Received 23 June 2008; received after revision 24 September 2008; accepted 30 September 2008 相似文献
8.
G. M. C. Janssen P. Schwertman T. A. T. Wanga R. S. Jahangir Tafrechi P. J. A. van den Broek A. K. Raap 《Cellular and molecular life sciences : CMLS》2009,66(4):721-730
Cytoplasmic translation is under sophisticated control but how cells adapt its rate to constitutive loss of mitochondrial
oxidative phosphorylation is unknown. Here we show that translation is repressed in cells with the pathogenic A3243G mtDNA
mutation or in mtDNA-less ρ0 cells by at least two distinct pathways, one transiently targeting elongation factor eEF-2 and the other initiation factor
eIF-2α constitutively. Under conditions of exponential cell growth and mammalian target of rapamycin (mTOR) activation, eEF-2
becomes transiently phosphorylated by an AMP-activated protein kinase (AMPK)-dependent pathway, especially high in mutant
cells. Independent of AMPK and mTOR, eIF-2α is constitutively phosphorylated in mutant cells, likely a signature of endoplasmic
reticulum (ER)-stress response induced by the loss of oxidative phosphorylation. While the AMPK/eEF-2K/eEF-2 pathway appears
to function in adaptation to physiological fluctuations in ATP levels in the mutant cells, the ER stress signified by constitutive
protein synthesis inhibition through eIF-2α-mediated repression of translation initiation may have pathobiochemical consequences.
Received 29 October 2008; received after revision 11 December 2008; accepted 16 December 2008 相似文献
9.
The Agouti-Related Protein (AgRP) is a powerful orexigenic peptide that increases food intake when ubiquitously overexpressed or when administered centrally. AgRP-deficiency, on the other hand, leads to increased metabolic rate and a longer lifespan when mice consume a high fat diet. In humans, AgRP polymorphisms have been consistently associated with resistance to fatness in Blacks and Whites and resistance to the development of type-2 diabetes in African Blacks. Systemically administered AgRP accumulates in the liver, the adrenal gland and fat tissue while recent findings suggest that AgRP may also have inverse agonist effects, both centrally and peripherally. AgRP could thus modulate energy balance via different actions. Its absence or reduced functionality may offer a benefit both in terms of bringing about negative energy balance in obesigenic environments, as well as leading to an increased lifespan. 相似文献
10.
Entry of herpesviruses into mammalian cells 总被引:4,自引:0,他引:4
The mechanism that herpesviruses use to enter cells is one of the most complex viral entry mechanisms studied so far. This complexity seems to mount as new participants, both cellular receptors and viral glycoproteins, are identified. Recent structural work on entry glycoproteins gD and gB from herpes simplex virus (HSV) 1 has illuminated the functional roles of these glycoproteins in the process of entry. In doing so, it provided information on the mechanism of two critical steps of HSV entry: receptor-mediated activation and membrane fusion. Remarkably, it is becoming clear that herpesviruses have a lot in common with other, simpler viruses. 相似文献
11.
A. Gerson-Gurwitz N. Movshovich R. Avunie V. Fridman K. Moyal B. Katz M. A. Hoyt L. Gheber 《Cellular and molecular life sciences : CMLS》2009,66(2):301-313
S. cerevisiae anaphase spindle elongation is accomplished by the overlapping function of dynein and the kinesin-5 motor proteins, Cin8
and Kip1. Cin8 and dynein are synthetically lethal, yet the arrest phenotypes of cells eliminated for their function had not
been identified. We found that at a non-permissive temperature, dyn1Δ cells that carry a temperature-sensitive cin8 – 3 mutation arrest at mid-anaphase with a unique phenotype, which we named TAN (two microtubule asters in one nucleus). These
cells enter anaphase, but fail to proceed through the slow phase of anaphase B. At a permissive temperature, dyn1Δ, cin8 – 3 or dyn1Δcin8 – 3 cells exhibit perturbed spindle midzone morphologies, with dyn1Δcin8 – 3 anaphase spindles also being profoundly bent and nonrigid. Sorbitol, which has been suggested to stabilize microtubules,
corrects these defects and suppresses the TAN phenotype. We conclude that dynein and Cin8 cooperate in anaphase midzone organization
and influence microtubule dynamics, thus enabling progression through the slow phase of anaphase B.
Received 10 August 2008; received after revision 22 October 2008; accepted 27 October 2008 相似文献
12.
Arachiche A Badirou I Dachary-Prigent J Garcin I Geldwerth-Feniger D Kerbiriou-Nabias D 《Cellular and molecular life sciences : CMLS》2008,65(23):3861-3871
Rapid Ca2+-dependent phospholipid (PL) reorganization (scrambling) at the plasma membrane is a mechanism common to hematopoietic cells
exposing procoagulant phosphatidylserine (PS). The aim of this research was to determine whether activation of the extracellular
signal-regulated kinase (ERK) pathway was required for PL scrambling, based on a single report analyzing both responses induced
by Ca2+ ionophores in megakaryoblastic HEL cells. Ca2+ ionophore-stimulated ERK phosphorylation was induced in platelets without external Ca2+, whereas exogenous Ca2+ entry was crucial for ERK activation in Jurkat T cells. In both cells, membrane scrambling only occurred following Ca2+ entry and was not blocked by inhibiting ERK phosphorylation. Furthermore, ERK proteins are strongly phosphorylated in transformed
B lymphoblastic cell lines, which do not expose PS in their resting state. Overall, the data demonstrated that ERK activation
and membrane scrambling are independent mechanisms.
A. Arachiche, I. Badirou: These authors contributed equally to this work.
Received 18 June 2008; received after revision 24 September 2008; accepted 1 October 2008 相似文献
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Lin CI Chen CN Huang MT Lee SJ Lin CH Chang CC Lee H 《Cellular and molecular life sciences : CMLS》2008,65(17):2740-2751
Lysophosphatidic acid (LPA) is a low-molecular-weight lipid growth factor, which binds to G-protein-coupled receptors. Previous studies have shown that LPA enhances vascular endothelial growth factor-A (VEGF-A) expression in cancer cells and promotes angiogenesis process. However, the roles of LPA in lymphatic vessel formation and lymphangiogenesis have not been investigated. Here, we demonstrated that LPA up-regulated VEGF-C mRNA and protein expressions in human umbilical vein endothelial cells (HUVECs). Furthermore, the expression levels of lymphatic markers, including Prox-1, LYVE-1 and podoplanin, were enhanced in LPA-stimulated tube forming endothelial cells in vitro and in vivo. Moreover, we showed that pretreatment with MAZ51, a VEGFR-3 kinase inhibitor, and introduction of VEGFR-3 siRNA suppressed LPA-induced HUVEC tube formation and lymphatic marker expressions. These results demonstrated that LPA enhances expression of lymphatic markers through activating VEGF-C receptors in endothelial cells. This study provides basic information that LPA might be a target for therapeutics against lymphangiogenesis and tumor metastasis. 相似文献
15.
Roth L Koncina E Satkauskas S Crémel G Aunis D Bagnard D 《Cellular and molecular life sciences : CMLS》2009,66(4):649-666
The semaphorin family is a large group of proteins controlling cell migration and axonal growth cone guidance. These proteins
are bi-functional signals capable of growth promotion or growth inhibition. Initially described in the nervous system, the
majority of studies related to semaphorins and semaphorin signalling are nowadays performed in model systems outside the nervous
system. Here, we provide an exhaustive review of the many faces of semaphorins both during developmental, regulatory and pathological
processes. Indeed, because of their crucial fundamental roles, the semaphorins and their receptors represent important targets
for the development of drugs directed at a variety of diseases.
Received 22 August 2008; received after revision 22 September 2008; accepted 24 September 2008
L. Roth, E. Koncina, S. Satkauskas: These authors contributed equally to this work. 相似文献
16.
Proliferating cell nuclear antigen: a proteomics view 总被引:3,自引:0,他引:3
Naryzhny SN 《Cellular and molecular life sciences : CMLS》2008,65(23):3789-3808
Proliferating cell nuclear antigen (PCNA), a cell cycle marker protein, is well known as a DNA sliding clamp for DNA polymerase
delta and as an essential component for eukaryotic chromosomal DNA replication and repair. Due to its mobility inside nuclei,
PCNA is dynamically presented in a soluble or chromatin-associated form. The heterogeneity and specific modifications of PCNA
may reflect its multiple functions and the presence of many binding partners in the cell. The recent proteomics approaches
applied to characterizing PCNA interactions revealed multiple PCNA partners with a wide spectrum of activity and unveiled
the possible existence of new PCNA functions. Since more than 100 PCNA-interacting proteins and several PCNA modifications
have already been reported, a proteomics point of view seems exactly suitable to better understand the role of PCNA in cellular
functions.
Received 29 May 2008; received after revision 7 July 2008; accepted 16 July 2008 相似文献
17.
Porcelli AM Ghelli A Iommarini L Mariani E Hoque M Zanna C Gasparre G Rugolo M 《Cellular and molecular life sciences : CMLS》2008,65(18):2943-2951
Human thyroid carcinoma XTC.UC1 cells harbor a homoplasmic frameshift mutation in the MT-ND1 subunit of respiratory complex
I. When forced to use exclusively oxidative phosphorylation for energy production by inhibiting glycolysis, these cells triggered
a caspase-independent cell death pathway, which was associated to a significant imbalance in glutathione homeostasis and a
cleavage of the actin cytoskeleton. Overexpression of the anti-apoptotic Bcl-2 protein significantly increased the level of
endogenous reduced glutathione, thus preventing its oxidation after the metabolic stress. Furthermore, Bcl-2 completely inhibited
actin cleavage and increased cell adhesion, but was unable to improve cellular viability. Similar effects were obtained when
XTC.UC1 cells were incubated with exogenous glutathione. We hence propose that Bcl-2 can safeguard cytoskeletal stability
through an antioxidant function.
Received 28 May 2008; received after revision 8 July 2008; accepted 29 July 2008 相似文献
18.
Role of full-length osteoprotegerin in tumor cell biology 总被引:1,自引:1,他引:0
G. Zauli E. Melloni S. Capitani P. Secchiero 《Cellular and molecular life sciences : CMLS》2009,66(5):841-851
Osteoprotegerin (OPG) is a soluble tumor necrosis factor receptor family member, which potently inhibits RANKL-mediated osteoclastogenesis.
Numerous constructs have been created for therapeutic purposes in which the heparin-binding and death homology domains of
OPG were removed and the remaining peptide (amino acids 22–194) was fused to the Fc domain of human IgG1 (OPG-Fc). The administration
of OPG-Fc efficiently counteracted bone loss in a variety of preclinical models of cancers. However, several in vitro studies have shown that native or recombinant full-length OPG not only neuralizes RANKL, but also the death-inducing ligand
TRAIL, suggesting that OPG might potentially counteract the anti-tumor activity of TRAIL. Additional evidence suggests that
full-length OPG possesses RANKL- and TRAIL-independent biological properties, mainly related to the promotion of endothelial
cell survival and angiogenesis. Finally, breast tumor cells overexpressing OPG have shown increased bone metastatic potential
in vivo. The relevance of these apparently conflicting findings in tumor cell biology is highlighted.
Received 2 September 2008; received after revision 29 September 2008; accepted 13 October 2008 相似文献
19.
P. Nincheri P. Luciani R. Squecco C. Donati C. Bernacchioni L. Borgognoni G. Luciani S. Benvenuti F. Francini P. Bruni 《Cellular and molecular life sciences : CMLS》2009,66(10):1741-1754
Sphingosine 1-phosphate (S1P) is a bioactive sphingolipid which regulates multiple biological parameters in a number of cell
types, including stem cells. Here we report, for the first time, that S1P dose-dependently stimulates differentiation of adipose
tissue-derived mesenchymal stem cells (ASMC) towards smooth muscle cells. Indeed, S1P not only induced the expression of smooth
muscle cell-specific proteins such as α-smooth muscle actin (αSMA) and transgelin, but also profoundly affected ASMC morphology
by enhancing cytoskeletal F-actin assembly, which incorporated αSMA. More importantly, S1P challenge was responsible for the
functional appearance of Ca2+ currents, characteristic of differentiated excitable cells such as smooth muscle cells. By employing various agonists and
antagonists to inhibit S1P receptor subtypes, S1P2 turned out to be critical for the pro-differentiating effect of S1P, while S1P3 appeared to play a secondary role. This study individuates an important role of S1P in AMSC which can be exploited to favour
vascular regeneration.
Received 06 March 2009; accepted 17 March 2009 相似文献
20.
Delgado M Pérez-Miguelsanz J Garrido F Rodríguez-Tarduchy G Pérez-Sala D Pajares MA 《Cellular and molecular life sciences : CMLS》2008,65(13):2080-2090
Wilson's disease is characterized by longterm hepatic accumulation of copper leading to liver disease with reduction of S-adenosylmethionine synthesis. However, the initial changes in this pathway remain unknown and constitute the objective of the present study. Using the Long Evans Cinnamon rat model, early alterations were detected in the mRNA and protein levels, as well as in the activities of several enzymes of the methionine cycle. Notably, the main change was a redox-mediated 80% decrease in the mRNA levels of the methionine adenosyltransferase regulatory subunit as compared to the control group. Moreover, changes in S-adenosylmethionine, S-adenosylhomocysteine, methionine and glutathione levels were also observed. In addition, in vitro experiments show that copper affects the activity and folding of methionine adenosyltransferase catalytic subunits. Taken together, these observations indicate that early copper accumulation alters methionine metabolism with a pattern distinct from that described previously for other liver diseases. 相似文献