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321.
Navarro S Aleu J Jiménez M Boix E Cuchillo CM Nogués MV 《Cellular and molecular life sciences : CMLS》2008,65(2):324-337
Human eosinophil cationic protein (ECP)/ ribonuclease 3 (RNase 3) is a protein secreted from the secondary granules of activated
eosinophils. Specific properties of ECP contribute to its cytotoxic activities associated with defense mechanisms. In this
work the ECP cytotoxic activity on eukaryotic cell lines is analyzed. The ECP effects begin with its binding and aggregation
to the cell surface, altering the cell membrane permeability and modifying the cell ionic equilibrium. No internalization
of the protein is observed. These signals induce cell-specific morphological and biochemical changes such as chromatin condensation,
reversion of membrane asymmetry, reactive oxygen species production and activation of caspase-3-like activity and, eventually,
cell death. However, the ribonuclease activity component of ECP is not involved in this process as no RNA degradation is observed.
In summary, the cytotoxic effect of ECP is attained through a mechanism different from that of other cytotoxic RNases and
may be related with the ECP accumulation associated with the inflammatory processes, in which eosinophils are present.
Received 26 October 2007; accepted 23 November 2007 相似文献
322.
323.
Oddi S Fezza F Pasquariello N De Simone C Rapino C Dainese E Finazzi-Agrò A Maccarrone M 《Cellular and molecular life sciences : CMLS》2008,65(5):840-850
Anandamide is a lipid messenger that carries out a wide variety of biological functions. It has been suggested that anandamide
accumulation involves binding to a saturable cellular component. To identify the structure(s) involved in this process, we
analyzed the intracellular distribution of both biotinylated and radiolabeled anandamide, providing direct evidence that lipid
droplets, also known as adiposomes, constitute a dynamic reservoir for the sequestration of anandamide. In addition, confocal
microscopy and biochemical studies revealed that the anandamide-hydrolase is also spatially associated with lipid droplets,
and that cells with a larger adiposome compartment have an enhanced catabolism of anandamide. Overall, these findings suggest
that adiposomes may have a critical role in accumulating anandamide, possibly by connecting plasma membrane to internal organelles
along the metabolic route of this endocannabinoid.
S. Oddi, F. Fezza: These authors contributed equally to the study. 相似文献
324.
Protease-activated receptors (PARs) play a clear role in the burst of inflammatory reactions and immune responses. However,
for PAR-3, the most elusive member of the PAR family, the functional role is still largely unclear. It has been claimed that
PAR-3 does not signal autonomously, although the wide expression of human PAR-3 indicates its important physiological roles.
We demonstrate that in HEK-293 cells, stably transfected with human PAR-3, thrombin induced calcium signaling, IL-8 gene expression
and IL-8 release. We confirmed this finding using human lung epithelial and human astrocytoma cells that express endogenous
PAR-3. Moreover, thrombin exposure of HEK-293 cells resulted in ERK1/2 activation coinciding with IL-8 release. The effects
of thrombin were not dependent on PAR-1 activation, as confirmed by PAR-1 gene silencing. Thus, we propose that PAR-3 is able
to signal autonomously to induce IL-8 release mediated by ERK1/2 phosphorylation, which contributes actively to inflammatory
responses.
Received 9 December 2007; received after revision 16 January 2008; accepted 18 January 2008 相似文献
325.
Molecular and Cellular Basis of Regeneration and Tissue Repair 总被引:3,自引:0,他引:3
Rossi L Salvetti A Batistoni R Deri P Gremigni V 《Cellular and molecular life sciences : CMLS》2008,65(1):16-23
Planarians possess amazing abilities to regulate tissue homeostasis and regenerate missing body parts. These features reside on the presence of a population of pluripotent/totipotent stem cells, the neoblasts, which are considered as the only planarian cells able to proliferate in the asexual strains. Neoblast distribution has been identified by mapping the cells incorporating bromodeoxyuridine, analyzing mitotic figures and using cell proliferation markers. Recently identified molecular markers specifically label subgroups of neoblasts, revealing thus the heterogeneity of the planarian stem cell population. Therefore, the apparent totipotency of neoblasts probably reflects the composite activities of multiple stem cell types. First steps have been undertaken to understand how neoblasts and differentiated cells communicate with each other to adapt the self-renewal and differentiation rates of neoblasts to the demands of the body. Moreover, the introduction of molecular resource database on planarians now paves the way to renewed strategies to understand planarian regeneration and stem cell-related issues. 相似文献
326.
Src-family kinases (SFKs) regulate different granulocyte and monocyte/macrophage responses. Accumulating evidence suggests that members of this family are implicated in signal transduction pathways regulating phagocytic cell migration and recruitment into inflammatory sites. Macrophages with a genetic deficiency of SFKs display marked alterations in cytoskeleton dynamics, polarization and migration. This same phenotype is found in cells with either a lack of SFK substrates and/or interacting proteins such as Pyk2/FAK, c-Cbl and p190RhoGAP. Notably, SFKs and their downstream targets also regulate monocyte recruitment into inflammatory sites. Depending on the type of assay used, neutrophil migration in vitro may be either dependent on or independent of SFKs. Also neutrophil recruitment in in vivo models of inflammation may be regulated differently by SFKs depending on the tissue involved. In this review we will discuss possible mechanisms by which SFKs may regulate phagocytic cell migratory abilities. 相似文献
327.
Molecular mechanisms of phagocytic uptake in mammalian cells 总被引:2,自引:1,他引:1
Groves E Dart AE Covarelli V Caron E 《Cellular and molecular life sciences : CMLS》2008,65(13):1957-1976
Phagocytosis is a highly conserved, complex process that has evolved to counter the constant threat posed by pathogens, effete cells and debris. Classically defined as a mechanism for internalising and destroying particles greater than 0.5 mum in size, it is a receptor-mediated, actin-driven process. The best-studied phagocytic receptors are the opsono-receptors, FcgammaR and CR3. Phagocytic uptake involves actin dynamics including polymerisation, bundling, contraction, severing and depolymerisation of actin filaments. Recent evidence points to the importance of membrane remodelling during phagocytosis, both in terms of changes in lipid composition and delivery of new membrane to the sites of particle binding. Here we review the molecular mechanisms of phagocytic uptake and some of the strategies developed by microbial pathogens to manipulate this process. 相似文献
328.
329.
Kao WH Klag MJ Meoni LA Reich D Berthier-Schaad Y Li M Coresh J Patterson N Tandon A Powe NR Fink NE Sadler JH Weir MR Abboud HE Adler SG Divers J Iyengar SK Freedman BI Kimmel PL Knowler WC Kohn OF Kramp K Leehey DJ Nicholas SB Pahl MV Schelling JR Sedor JR Thornley-Brown D Winkler CA Smith MW Parekh RS;Family Investigation of Nephropathy Diabetes Research Group 《Nature genetics》2008,40(10):1185-1192
As end-stage renal disease (ESRD) has a four times higher incidence in African Americans compared to European Americans, we hypothesized that susceptibility alleles for ESRD have a higher frequency in the West African than the European gene pool. We carried out a genome-wide admixture scan in 1,372 ESRD cases and 806 controls and found a highly significant association between excess African ancestry and nondiabetic ESRD (lod score = 5.70) but not diabetic ESRD (lod = 0.47) on chromosome 22q12. Each copy of the European ancestral allele conferred a relative risk of 0.50 (95% CI = 0.39-0.63) compared to African ancestry. Multiple common SNPs (allele frequencies ranging from 0.2 to 0.6) in the gene encoding nonmuscle myosin heavy chain type II isoform A (MYH9) were associated with two to four times greater risk of nondiabetic ESRD and accounted for a large proportion of the excess risk of ESRD observed in African compared to European Americans. 相似文献
330.
Two major functions of the Golgi apparatus (GA) are formation of complex glycans and sorting of proteins destined for various
subcellular compartments or secretion. To fulfill these tasks proper localization of the accessory proteins within the different
sub-compartments of the GA is crucial. Here we investigate structural determinants mediating transition of the two glycosyltransferases
β-1,4- galactosyltransferase 1 (gal-T1) and the α-1,3-fucosyltransferase 6 (fuc-T6) from the trans-Golgi cisterna to the trans-Golgi network (TGN). Upon treatment with the ionophore monensin both glycosyltransferases are found in TGN-derived swollen
vesicles, as determined by confocal fluorescence microscopy and density gradient fractionation. Both enzymes carry a signal
consisting of the amino acids E5P6 in gal-T1 and D2P3 in fuc-T6 necessary for the transition of these glycosyltransferases from the trans-Golgi cisterna to the TGN, but not for their steady state localization in the trans-Golgi cisterna.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.
Received 30 July 2008; received after revision 17 September 2008; accepted 29 September 2008 相似文献