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41.
The bovine vitreous-derived lipid factor (bVLF) is a powerful inhibitor of retinal pigmented epithelial (hRPE) cell proliferation 总被引:3,自引:0,他引:3
Human retinal pigmented epithelial cell (hRPE) proliferation plays a significant role in various proliferative diseases associated to the retina that leads to loss of vision, such as proliferative vitreoretinopathy. In the current study, the role of the bovine vitreous lipid factor (bVLF) in hRPE cell proliferation has been investigated. bVLF is a bioactive lipid isolated from the bovine vitreous body with strong Ca(2+)-mobilizing activity in fibroblast. In the first approach, the effects of bVLF on Ca(2+)-mobilizing activity were investigated in hRPE. The results showed that bVLF induced, in a dose-dependent manner, a Ca(2+) mobilization from PA-sensitive intracellular stores [non-Ins(1,4,5)P(3)-sensitive stores], in which extracellular Ca(2+) participated. The increase in intracellular Ca(2+) was associated with a dose-dependent inhibiting effect on cell proliferation. At a dose of 10 microg/mL, bVLF caused a 26% or a 44% inhibition in hRPE cell proliferation during the 3- or the 6-day culture periods, respectively. These effects appear to be specific in hRPE cells, since EFGR-T17 fibroblast cells treated with equivalent amounts of bVLF did not show any inhibiting effects. This inhibitory action was not associated to apoptotic/necrotic processes. Furthermore, bVLF inhibited EGF-, bFGF-, IGF-I-, PDGF-, HGF- and VEGF-induced proliferation of the hRPE cells. Moreover, this inhibitory response was also observed in FBS-induced hRPE cell proliferation. bVLF, at a concentration of 10 microg/mL, induced 16% inhibition of proliferation during a culture period of 3 days. This inhibitory action was greater during the 6-day culture period, exceeding 40%. With regard to this action, the results showed that bVLF has a potent inhibitory effect on ERK1/2 activation, and plays a key role in the control of hRPE cell proliferation. These observations contribute to the knowledge of inhibitory factors responsible for keeping antiproliferative environment that preserve the RPE-associated activities in normal states. It advances the interesting possibility that this factor or a factor with characteristics common to bVLF might be involved in the pathogenesis of abnormal proliferative eye processes. 相似文献
42.
Grifolin is a natural biologically active substance isolated from the fresh fruiting bodies of the mushroom Albatrellus confluens. Here, for the first time, we describe a novel activity of grifolin, namely its ability to inhibit the growth of tumor cells by the induction of apoptosis. Grifolin strongly inhibited the growth of tumor cell lines: CNE1, HeLa, MCF7, SW480, K562, Raji and B95-8. Analysis of acridine orange (AO)/ethidium bromide (EB) staining and flow cytometry showed that grifolin possessed apoptosis induction activity to CNE1, HeLa, MCF7 and SW480. Furthermore, the cytochrome c release from mitochondria was detected by confocal microscopy in CNE1 cells after a 12h treatment with grifolin. The increase of caspase-8, 9, 3 activities revealed that caspase was a key mediator of the apoptotic pathway induced by grifolin, and the underexpression of Bcl-2 and up-regulation of Bax resulted in the increase of Bax: Bcl-2 ratio, suggesting that Bcl-2 family involved in the control of apoptosis. Owing to the combination of the significant antitumor activity by inducing apoptosis and natural abundance of the compound, grifolin holds the promise of being an interesting antitumor agent that deserves further laboratory and in vivo exploration. 相似文献
43.
Effects of T8993G mutation in mitochondrial DNA (mtDNA), associated with neurogenical muscle weakness, ataxia and retinitis pigmentosa (NARP), on the cytoskeleton, mitochondrial network and calcium homeostasis in human osteosarcoma cells were investigated. In 98% NARP and rho(0) (lacking mtDNA) cells, the organization of the mitochondrial network and actin cytoskeleton was disturbed. Capacitative calcium entry (CCE) was practically independent of mitochondrial energy status in osteosarcoma cell lines. The significantly slower Ca(2+) influx rates observed in 98% NARP and rho(0), in comparison to parental cells, indicates that proper actin cytoskeletal organization is important for CCE in these cells. 相似文献
44.
Human Tid-1 (hTid-1) is a DnaJ chaperone protein with homology to the Drosophila tumor suppressor Tid56. We report the first case of a tumor-associated mutation at the human TID1 locus, which was identified in the SF767 glioma cell line giving rise to aberrantly high levels of a hTid-1(L) mutant variant. In this study, we set out to determine whether this change in hTid-1 status influences the response of glioma cells to adenoviral (Ad)-mediated delivery of the two major isoforms of TID1, hTid-1(L) and hTid-1(S). Ad-hTid-1(S) induced apoptosis in hTid-1 mutant SF767 cells, while causing growth arrest in wild-type hTid-1-expressing U373 and U87 cells. By contrast, Ad-hTid-1(L) infection had no apparent effect on glioma cell growth. The apoptosis induced by hTid-1(S) was accompanied by mitochondrial cytochrome C release and caspase activation and blocked by stable overexpression of Bcl-X(L). Our findings suggest that the status of hTid-1 in gliomas may contribute to their susceptibility to cell death triggers. 相似文献
45.
Dynamic iodide trapping by tumor cells expressing the thyroidal sodium iodide symporter 总被引:1,自引:0,他引:1
Dingli D Bergert ER Bajzer Z O'connor MK Russell SJ Morris JC 《Biochemical and biophysical research communications》2004,325(1):157-166
The thyroidal sodium iodide symporter (NIS) in combination with various radioactive isotopes has shown promise as a therapeutic gene in various tumor models. Therapy depends on adequate retention of the isotope in the tumor. We hypothesized that in the absence of iodide organification, isotope trapping is a dynamic process either due to slow efflux or re-uptake of the isotope by cells expressing NIS. Iodide efflux is slower in ARH-77 and K-562 cells expressing NIS compared to a thyroid cell line. Isotope retention half times varied linearly with the number of cells expressing NIS. With sufficient NIS expression, iodide efflux is a zero-order process. Efflux kinetics in the presence or absence of perchlorate also supports the hypothesis that iodide re-uptake occurs and contributes to the retention of the isotope in tumor cells. Iodide organification was insignificant. In vivo studies in tumors composed of mixed cell populations confirmed these observations. 相似文献
46.
47.
Boray Nguyen 《Journal of molecular biology》2010,397(5):1245-21705
Elongation factor G (EF-G) is one of several GTP hydrolytic proteins (GTPases) that cycles repeatedly on and off the ribosome during protein synthesis in bacterial cells. In the functional cycle of EF-G, hydrolysis of guanosine 5′-triphosphate (GTP) is coupled to tRNA-mRNA translocation in ribosomes. GTP hydrolysis induces conformational rearrangements in two switch elements in the G domain of EF-G and other GTPases. These switch elements are thought to initiate the cascade of events that lead to translocation and EF-G cycling between ribosomes. To further define the coupling mechanism, we developed a new fluorescent approach that can detect intramolecular movements in EF-G. We attached a fluorescent probe to the switch I element (sw1) of Escherichia coli EF-G. We monitored the position of the sw1 probe, relative to another fluorescent probe anchored to the GTP substrate or product, by measuring the distance-dependent, Förster resonance energy transfer between the two probes. By analyzing EF-G trapped at five different functional states in its cycle, we could infer the cyclical movements of sw1 within EF-G. Our results provide evidence for conformational changes in sw1, which help to drive the unidirectional EF-G cycle during protein synthesis. More generally, our approach might also serve to define the conformational dynamics of other GTPases with their cellular receptors. 相似文献
48.
Paolo Paoli Francesca Sbrana Anna Caselli Paolo Cirri Lucia Formigli Giampaolo Manao Giampietro Ramponi 《Journal of molecular biology》2010,400(4):889-907
Previous works reported that a mild increase in homocysteine level is a risk factor for cardiovascular and neurodegenerative diseases in humans. Homocysteine thiolactone is a cyclic thioester, most of which is produced by an error-editing function of methionyl-tRNA synthetase, causing in vivo post-translational protein modifications by reacting with the ?-amino group of lysine residues. In cells, the rate of homocysteine thiolactone synthesis is strictly dependent on the levels of the precursor metabolite, homocysteine. In this work, using bovine serum albumin as a model, we investigated the impact of N-homocysteinylation on protein conformation as well as its cellular actions. Previous works demonstrated that protein N-homocysteinylation causes enzyme inactivation, protein aggregation, and precipitation. In addition, in the last few years, several pieces of evidence have indicated that protein unfolding and aggregation are crucial events leading to the formation of amyloid fibrils associated with a wide range of human pathologies. For the first time, our results reveal how the low level of protein N-homocysteinylation can induce mild conformational changes leading to the formation of native-like aggregates evolving over time, producing amyloid-like structures. Taking into account the fact that in humans about 70% of circulating homocysteine is N-linked to blood proteins such as serum albumin and hemoglobin, the results reported in this article could have pathophysiological relevance and could contribute to clarify the mechanisms underlying some pathological consequences described in patients affected by hyperhomocysteinemia. 相似文献
49.
TIP47 protects mitochondrial membrane integrity and inhibits oxidative-stress-induced cell death 总被引:1,自引:0,他引:1
E. Hocsak A. Szabo E. Rapolti Sz. Javor F. Gallyas Jr. A. Szigeti 《FEBS letters》2010,584(13):2953-2960
We found that overexpression of tail interacting protein of 47 kDa (TIP47), but not its truncated form (t-TIP47) protected NIH3T3 cells from hydrogen-peroxide-induced cell death, prevented the hydrogen-peroxide-induced mitochondrial depolarization determined by 5,5′,6,6′-tetrachloro-1,1′,3,3′-tetraethyl-benzimidazolylcarbocyanine iodide (JC1), while suppression of TIP47 in HeLa cells facilitated oxidative-stress-induced cell death. TIP47 was located to the cytoplasm of untreated cells, but some was associated to mitochondria in oxidative stress. Recombinant TIP47, but not t-TIP47 increased the mitochondrial membrane potential (Δψ), and partially prevented Ca2+ induced depolarization. It is assumed that TIP47 can bind to mitochondria in oxidative stress, and inhibit mitochondria mediated cell death by protecting mitochondrial membrane integrity. 相似文献
50.
Eszter Doma 《FEBS letters》2010,584(5):1033-1040
The activation of cysteine-aspartic proteases or caspases and the dynamic arrangement of cytoskeletal components are crucial during apoptosis. Here we describe the fate of Fas downstream of the FasL-induced internalization step, including formation of caspase-dependent SDS-stable Fas complexes, which is mediated by cytoskeleton integrity. We show, in particular, that following FasL treatment, the Fas lower aggregate complex can be co-immunoprecipitated with tubulin and an active form of caspase-8 and that this interaction contributes to the propagation of FasL-induced cell death. The importance of cytoskeletal components during FasL-induced apoptosis is highlighted by our detection of a pool of microtubule-associated Fas complexes. 相似文献