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1.
Phosphatidylinositol 3-kinase (PI3-kinase) activity has been implicated in regulating cell cycle progression at distinct points
in the cell cycle by preventing cell cycle arrest or apoptosis. In this study, the role of PI3-kinase activity during the
entire G1 phase of the ongoing cell cycle was studied in Chinese hamster ovary (CHO) cells synchronized by mitotic shake-off.
We show that inhibition of PI3-kinase activity during and 2 h after mitosis inhibited cell cycle progression into S phase.
In the presence of the PI3-kinase inhibitor wortmannin or LY294002, cells were arrested during early G1 phase, leading to
the expression of the cleaved caspase-3, a central mediator of apoptosis. These results demonstrate that PI3-kinase activity
is required for progression through the M/G1 phase. In the absence of PI3-kinase activity, cells are induced for apoptosis
in this particular phase of the cell cycle.
Received 7 September 2005; received after revision 26 October 2005; accepted 11 November 2005 相似文献
2.
Rivera A Mavila A Bayless KJ Davis GE Maxwell SA 《Cellular and molecular life sciences : CMLS》2006,63(12):1425-1439
We were the first to identify cyclin A1 as a p53-induced gene by cDNA expression profiling of p53-sensitive and -resistant
tumor cells [Maxwell S. A. and Davis G. E. (2000) Proc. Natl. Acad. Sci. USA 97, 13009–13014]. We show here that cyclin A1
can induce G2 cell cycle arrest, polyploidy, apoptosis, and mitotic catastrophe in H1299 non-small cell lung, TOV-21G ovarian,
or 786-0 renal carcinoma cells. More cdk1 protein and kinase activities were observed in cyclin A1-induced cells than in GFP
control-induced cells. Thus, cyclin A1 might mediate apoptosis and mitotic catastrophe through an unscheduled or inappropriate
activation of cdk1. Two primary renal cell carcinomas expressing mutated p53 exhibited reduced or absent expression of cyclin
A1 relative to the corresponding normal tissue. Moreover, renal carcinoma-derived mutant p53s were deficient in inducing cyclin
A1 expression in p53-null cells. Cyclin A1 but not cyclin A2 was upregulated in etoposide-treated tumor cells undergoing p53-dependent
apoptosis and mitotic catastrophe. Forced upregulation of cyclin A2 did not induce apoptosis. The data implicate cyclin A1
as a downstream player in p53-dependent apoptosis and G2 arrest.
Received 1 November 2005; received after revision 17 February 2006; accepted 13 April 2006 相似文献
3.
Albrecht M Frungieri MB Kunz L Rämsch R Meineke V Köhn FM Mayerhofer A 《Cellular and molecular life sciences : CMLS》2005,62(23):2867-2876
Fibroblast proliferation is a key process in tissue remodeling and mast cells (MCs) are thought to play a crucial role. Having
established that the three major MC products, tryptase, histamine and TNF-alpha (TNF) are normally present in human skin MCs,
which are in close proximity to dermal fibroblasts, we studied their individual effects on cell cycle-controlled human dermal
fibroblasts (HFFF2). These cells express receptors (H1, PAR2, TNFR1/2) for the major MC mediators, but only tryptase or a
PAR2 agonist peptide stimulated proliferation and gene expression. TNF was antimitotic, and histamine, while elevating intracellular
Ca2+ levels at high concentrations, did not affect proliferation. We conclude that MC products but also composition and numbers
of respective receptors on fibroblasts are crucially responsible for fibroproliferative events.
Received: 28 June 2005; received after revision 28 September 2005; accepted 6 October 2005 相似文献
4.
5.
Caron L Prot M Rouleau M Rolando M Bost F Binétruy B 《Cellular and molecular life sciences : CMLS》2005,62(14):1605-1612
Control of mammalian gene promoters by the bacterial LacI repressor provides reversible regulation and dose-response levels of derepressed expression by the lactose analog isopropyl thiogalactose (IPTG). Here, we show that insertion of LacI-binding sites in the ubiquitous β-actin promoter confers a strong and dose-dependent IPTG-regulatable expression of transiently transfected reporter genes in mouse embryonic stem (ES) cells expressing LacI. We established ES cell lines stably expressing reporter genes under inducible control and found a five- to tenfold IPTG induction of transgene expression. The kinetics of induction is rapid and stable, and can be rapidly reversed after IPTG removal. Importantly, this regulatable expression was maintained throughout the differentiation process of ES cells, and observed in individual differentiated cardiomyocyte-like cells and neuronal-like cells. This reversible system is the first to function from undifferentiated to individual welldifferentiated ES cells, providing a very useful tool to understand molecular mechanisms underlying ES cell self-renewal, commitment and differentiation.Received 17 March 2005; received after revision 19 April 2005; accepted 25 April 2005 相似文献
6.
Koleva M Kappler R Vogler M Herwig A Fulda S Hahn H 《Cellular and molecular life sciences : CMLS》2005,62(16):1863-1870
Muscle satellite cells are believed to form a stable, self-renewing pool of stem cells in adult muscle where they function in tissue growth and repair. A regulatory disruption of growth and differentiation of these cells is assumed to result in tumor formation. Here we provide for the first time evidence that sonic hedgehog (Shh) regulates the cell fate of adult muscle satellite cells in mammals. Shh promotes cell division of satellite cells (and of the related model C2C12 cells) and prevents their differentiation into multinucleated myotubes. In addition, Shh inhibits caspase-3 activation and apoptosis induced by serum deprivation. These effects of Shh are reversed by simultaneous administration of cyclopamine, a specific inhibitor of the Shh pathway. Taken together, Shh acts as a proliferation and survival factor of satellite cells in the adult muscle. Our results support the hypothesis of the rhabdomyosarcoma origin from satellite cells and suggest a role for Shh in this process.Received 23 February 2005; received after revision 2 May 2005; accepted 9 June 2005 相似文献
7.
Pani A Batetta B Putzolu M Sanna F Spano O Piras S Mulas MF Bonatesta RR Amat di S Filippo C Vargiu L Marceddu T Sanna L La Colla P Dessì S 《Cellular and molecular life sciences : CMLS》2000,57(7):1094-1102
The product of the MDR1 gene (P-gp) has been implicated in the transport of cholesterol from plasma membrane to endoplasmic reticulum for esterification.
In previous studies on leukemia cell lines, we suggested that cholesterol esterification may regulate the rate of cell growth
and that the MDR1 gene might be involved in this process by modulating intracellular cholesterol esters levels. To further investigate this
matter, the rate of cell growth, cholesterol metabolism, expression of the MDR1 gene, and P-gp activity were compared in KB cell lines displaying differences in expression and function of P-gp (drug-sensitive
phenotype versus MDR phenotype). The rate of cell growth correlated with cholesterol esterification in all KB cell lines,
whereas the over-expression of MDR1 observed in the MDR cell lines was not always associated with an increased capacity of cells to esterify cholesterol. Two
known inhibitors of P-gp activity, progesterone and verapamil, strongly inhibited both cholesterol esterification and cell
proliferation in all KB cell lines, but they affected intracellular accumulation of labeled vinblastine only in MDR cell lines.
These results further support a role for cholesterol esters in the regulation of cell growth and suggest that the P-gp expressed
in MDR KB cells is not involved in the general process leading to cholesterol esterification.
Received 14 February 2000; received after revision 10 April 2000; accepted 8 May 2000 相似文献
8.
Major contribution of codominant CD8 and CD4 T cell epitopes to the human cytomegalovirus-specific T cell repertoire 总被引:3,自引:0,他引:3
Nastke MD Herrgen L Walter S Wernet D Rammensee HG Stevanović S 《Cellular and molecular life sciences : CMLS》2005,62(1):77-86
Human cytomegalovirus (HCMV) infection or reactivation is a cause of morbidity and mortality in immunocompromised individuals. In immunocompetent individuals, in contrast, HCMV is successfully controlled by specific CD8 and CD4 T cells. Knowledge of CD8 and CD4 T cell epitopes from HCMV and their immunodominant features is crucial for the generation of epitope-specific T cells for adoptive immunotherapy and for the development of a peptide-based HCMV vaccine. Therefore, we investigated the natural frequencies of a large number of CD8 and CD4 T cell epitopes, including 10 novel ones. We determined several epitopes as immunodominant. Surprisingly, no clear hierarchies were found for CD8 T cell epitopes, indicating codominance. These results will be valuable for adoptive transfer strategies and support initiatives towards development of a peptide-based HCMV vaccine.Received 12 August 2004; received after revision 24 September 2004; accepted 29 October 2004 These authors contributed equally to this work. 相似文献
9.
摘要:目的提取弓形虫体外细胞共培养上清,并研究上清对人急性单核细胞白血病细胞THP-1增殖及凋亡的影响。方法收集对数生长期的THP-1细胞以5X10^7/ml细胞浓度接种于不同培养瓶中,对照组加入含10%胎牛血清的RPMll640,实验组加入相同体积不同数量(2×10^7/ml、4X10^7/ml、8×10^7/m1)弓形虫速殖子培养上清,采用四甲基氮噻唑蓝(MTY)法检测吸光度(A490值)并计算THP-1细胞增殖抑制率;倒置显微镜下观察细胞形态变化;Annexin-V-FITC/PI染色细胞后上流式细胞仪检测各个时间点细胞凋亡率变化,以Western印迹方法分析凋亡相关蛋白Bax、Bcl-2的表达或活性。结果MTY法检测结果弓形虫培养上清呈时间剂量依赖性抑制THP-1细胞株增殖,倒置显微镜下观察处理组细胞有发泡现象和凋亡小体出现。流式细胞仪检测弓形虫感染后的THP-1细胞凋亡率较对照组有升高趋势(P〈0.05),呈量效依赖性,Westernblot检测刚地弓形虫培养上清作用于THP-l细胞48h后实验组的Bax、Bcl-2蛋白表达较对照组的比值分别有明显的升高与降低(P〈0.05)。结论刚地弓形虫速殖子培养上清对体外培养THP-l细胞增殖有明显的抑制作用,并可诱导THP-1细胞凋亡。 相似文献
10.
Regulation of neutrophil apoptosis via death receptors 总被引:4,自引:0,他引:4
11.
MDA-MB-468 is a human mammary adenocarcinoma cell line that overexpresses the epidermal growth factor (EGF) receptor and
undergoes programmed cell death (apoptosis) in response to EGF treatment. Programmed cell death was shown to be greatly enhanced
when cells were growth-arrested prior to EGF treatment. Apoptosis was characterized by an initial rounding up and detachment
of the cells from their substrate starting about 12 h after EGF treatment, followed by chromatin condensation, nuclear fragmentation
and oligonucleosomal fragmentation of the DNA at about 24 to 48 h. Cell death was dependent on de novo protein synthesis.
We found a rapid induction of c-fos, c-jun and junB at the mRNA level after about 30 min of EGF treatment and a more delayed upregulation of fosB and fra-1. The junD gene was expressed in the absence of EGF, and it was moderately induced within 30 min of growth factor addition. The increase
of the different fos and jun mRNAs were paralleled by an increase of activator protein-1 (AP-1) DNA binding activity. A characterization of the AP-1 complex
revealed similar levels of several Fos and Jun proteins. Based on the kinetics of AP-1 accumulation and cell death, it seems
likely that AP-1 contributes to the apoptotic cell death of EGF receptor-overexpressing MDA-MB-468 cells.
Received 21 July 1997; received after revision 6 November 1997; accepted 6 November 1997 相似文献
12.
Leizerman I Avunie-Masala R Elkabets M Fich A Gheber L 《Cellular and molecular life sciences : CMLS》2004,61(16):2060-2070
The kinesin-related protein HsEg5 plays essential roles in mitotic spindle dynamics. Although inhibition of HsEg5 has been suggested as an aid in cancer treatment, the effects of such inhibition on human cells have not been characterized. Here we studied the effects of monastrol, an allosteric HsEg5 inhibitor, on AGS and HT29 cell lines and compared them to those of taxol. While both cell lines were similarly sensitive to taxol, AGS cells were more sensitive to monastrol. The differences in sensitivity were determined by the degree of inhibitory effect on cell proliferation, reversibility of monastrol-induced G2/M arrest, intracellular phenotypes and induction of apoptosis. In both cell lines, monastrol-induced apoptosis was accompanied by mitochondrial membrane depolarization and poly-ADP-ribose polymerase 1 cleavage. In AGS, but not HT29 cells, monastrol-induced apoptosis involved a prominent cleavage of procaspases 8 and 3. While in AGS cells, monastrol induced the formation of symmetric microtubule asters only, in HT29 cells, asymmetric asters were also formed, which may be related to specific HsEg5 functions in HT29 cells.Received 18 February 2004; received after revision 30 May 2004; accepted 16 June 2004 相似文献
13.
Galectins in cell growth and apoptosis 总被引:23,自引:0,他引:23
Fourteen members of the galectin family, proteins with conserved carbohydrate-recognition domains that bind β-galactoside,
have been cloned and more are expected to be discovered in the near future. Many aspects of galectin biology have been thoroughly
explored, and functional studies have implicated these proteins in cell growth, differentiation and apoptosis, in addition
to cell adhesion, chemoattraction and cell migration. In some cases a galectin can either promote or suppress cell growth,
depending on the cell types and doses used. Galectin-3 is the only member known so far to inhibit apoptosis, while galectin-1,
-7 and -9 promote this cellular process. Galectins can act either extracellularly or intracellularly to exert effects on cell
growth and apoptosis.
RID="*"
ID="*"Corresponding author. 相似文献
14.
Emodin inhibits tumor cell migration through suppression of the phosphatidylinositol 3-kinase-Cdc42/Rac1 pathway 总被引:6,自引:0,他引:6
Enhanced cell migration is one of the underlying mechanisms in cancer invasion and metastasis. Therefore, inhibition of cell migration is considered to be an effective strategy for prevention of cancer metastasis. We found that emodin (3-methyl-1,6,8-trihydroxyanthraquinone), an active component from the rhizome of Rheum palmatum, significantly inhibited epidermal growth factor (EGF)- induced migration in various human cancer cell lines. In the search for the underlying molecular mechanisms, we demonstrated that phosphatidylinositol 3-kinase (PI3K) serves as the molecular target for emodin. In addition, emodin markedly suppressed EGF-induced activation of Cdc42 and Rac1 and the corresponding cytoskeleton changes. Moreover, emodin, but not LY294002, was able to block cell migration in cells transfected with constitutively active (CA)-Cdc42 and CA-Rac1 by interference with the formation of Cdc42/Rac1 and the p21-activated kinase complex. Taken together, data from this study suggest that emodin inhibits human cancer cell migration by suppressing the PI3K-Cdc42/Rac1 signaling pathway.Received 7 February 2005; received after revision 11 March 2005; accepted 18 March 2005 相似文献
15.
Stem cells and their niche: a matter of fate 总被引:4,自引:0,他引:4
Embryonic stem cells provide an in vitro model for developmental biologists to study cell fate decisions during ontogenesis, while somatic stem cells allow physiologists
to understand tissue homeostasis in the adult. The behavior of stem cells is dependent on an intimate relationship with a
supportive niche. This brief review highlights some of the most important recent trends in stem cell biology, focusing in
particular on the supportive microenvironments for both embryonic and adult stem cells. Known intrinsic and extrinsic molecular
players from the best-characterized stem cell types are summarized, illuminating a number of shared environmental cues among
tissues originating from all three embryonic germ layers.
Received 6 October 2005; received after revision 27 December 2005; accepted 17 January 2006 相似文献
16.
Corti S Salani S Del Bo R Torrente Y Strazzer S Belicchi M Paganoni S Li Z Comi GP Bresolin N Paulin D Scarlato G 《Cellular and molecular life sciences : CMLS》2001,58(1):135-140
The generation of human myogenic cell lines could potentially provide a valuable source for cell transplantation in myopathies. The dysregulation of proliferative-differentiative signals by viral oncogenes can result in the induction of apoptosis. Whether apoptosis occurred in myogenic cells expressing large T antigen (Tag) from SV40 upon differentiation was unknown. Human muscle satellite cells were transfected with two different constructs, containing either an origin-defective SV40 genome or Tag under vimentin promoter control. When differentiation was triggered, Tag expression reduced the formation of myotubes and dead cells showing apoptotic features were present. However, the cells expressing SV40 Tag under vimentin promoter control retained their capacity to form myotubes and expressed the myofibrillar proteins as myosin heavy chain and dystrophin when Tag expression was silent. Their apoptotic rate was similar to that of untransfected cells. The observation that apoptosis can be prevented by the down-regulation of Tag suggests that the programmed cell death induced in transformed cells can be reversed, and confirms the regulatory efficiency of the human vimentin promoter. 相似文献
17.
Glucocorticoids in T cell apoptosis and function 总被引:5,自引:0,他引:5
Glucocorticoids (GCs) are a class of steroid hormones which regulate a variety of essential biological functions. The profound
anti-inflammatory and immunosuppressive activity of synthetic GCs, combined with their power to induce lymphocyte apoptosis
place them among the most commonly prescribed drugs worldwide. Endogenous GCs also exert a wide range of immunomodulatory
activities, including the control of T cell homeostasis. Most, if not all of these effects are mediated through the glucocorticoid
receptor, a member of the nuclear receptor superfamily. However, the signaling pathways and their cell type specificity remain
poorly defined. In this review, we summarize our present knowledge on GC action, the mechanisms employed to induce apoptosis
and the currently discussed models of how they may participate in thymocyte development. Although our knowledge in this field
has substantially increased during recent years, we are still far from a comprehensive picture of the role that GCs play in
T lymphocytes.
Received 20 August 2005; received after revision 27 September 2005; accepted 10 October 2005 相似文献
18.
Protein farnesylation in mammalian cells: effects of farnesyltransferase inhibitors on cancer cells 总被引:3,自引:0,他引:3
F. Tamanoi C.-L. Gau C. Jiang H. Edamatsu J. Kato-Stankiewicz 《Cellular and molecular life sciences : CMLS》2001,58(11):1636-1649
Protein farnesylation, catalyzed by protein farnesyltransferase, plays important roles in the membrane association and protein-protein
interaction of a number of eukaryotic proteins. Recent development of farnesyltransferase inhibitors (FTIs) has led to further
insight into the biological significance of farnesylation in cancer cells. A number of reports point to the dramatic effects
FTIs exert on cancer cells. In addition to inhibiting anchorage-independent growth, FTIs cause changes in the cell cycle either
at the G1/S or at the G2/M phase. Furthermore, induction of apoptosis by FTIs has been reported. FTIs also affects the actin
cytoskeleton and cell morphology. This review summarizes these reports and discusses implications for farnesylated proteins
responsible for these FTI effects.
Received 17 April 2001; received after revision 28 May 2001; accepted 28 May 2001 相似文献
19.
A population of uterine natural killer (NK) cells, commonly called granulated metrial gland (GMG) cells, differentiates in the mouse uterus during normal pregnancy. Little is known regarding the process of differentiation of GMG cells or of other NK cell subsets. It has been suggested that macrophage precursors, under the combined influences of the cytokine growth factors colony stimulating factor-1 (CSF-1) and interleukin-2, become NK-cell like in morphology, pattern of target cell lysis and surface antigen phenotype. Mice expressing the mutation osteopetrosis (op/op) are unable to produce the cytokine CSF-1. To determine whether CSF-1 is required for the successful differentiation of uterine NK cells, implantation sites in pregnant,op/op mice were studied histologically. GMG cell differentiation appeared to progress normally inop/op mice studied between days 7 and 14 of gestation. Thus, the growth factor CSF-1 is not required for differentiation of the uterine NK cell subset known as GMG cells and probably GMG cells do not differentiate from macrophage precursor cells which are deficient inop/op mice. 相似文献
20.
Interleukin-17 stimulates inducible nitric oxide synthase-dependent toxicity in mouse beta cells 总被引:2,自引:0,他引:2
Miljkovic D Cvetkovic I Momcilovic M Maksimovic-Ivanic D Stosic-Grujicic S Trajkovic V 《Cellular and molecular life sciences : CMLS》2005,62(22):2658-2668
The influence of the proinflammatory cytokine interleukin (IL)-17 on inducible nitric oxide (NO) synthase (iNOS)-mediated
NO release was investigated in the mouse insulinoma cell line MIN6 and mouse pancreatic islets. IL-17 markedly augmented iNOS
mRNA/protein expression and subsequent NO production induced in MIN6 cells or pancreatic islets by different combinations
of interferon-γ, tumor necrosis factor-α, and IL-1β. The induction of iNOS by IL-17 was preceded by phosphorylation of p38
mitogen-activated protein kinase (MAPK), and inhibition of p38 MAPK activation completely abolished IL-17-stimulated NO release.
IL-17 enhanced the NO-dependent toxicity of proinflammatory cytokines toward MIN6 cells, while IL-17-specific neutralizing
antibody partially reduced the NO production and rescued insulinoma cells and pancreatic islets from NO-dependent damage induced
by activated T cells. Finally, a significant increase in blood IL-17 levels was observed in a multiple low-dose streptozotocin
model of diabetes, suggesting that T cell-derived IL-17 might be involved in NO-dependent damage of beta cells in this disease.
Received 14 June 2005; received after revision 17 September 2005; accepted 21 September 2005 相似文献