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1.
Interaction of galectin-1 with caveolae induces mouse embryonic stem cell proliferation through the Src, ERas, Akt and mTOR signaling pathways 总被引:1,自引:0,他引:1
M. Y. Lee S. H. Lee J. H. Park H. J. Han 《Cellular and molecular life sciences : CMLS》2009,66(8):1467-1478
Galectins have the potential to provide a promising alternative for unveiling the complexity of embryonic stem (ES) cell self-renewal,
although the mechanism by which galectins maintain ES cell self-renewal has yet to be identified. Galectin-1 increased [3H]-thymidine incorporation as well as cyclin expression and decreased p27kip1 expression. Src and caveolin-1 phosphorylation was increased by galectin-1, and phospho-caveolin-1 was inhibited by PP2.
In addition, inhibition of caveolin-1 by small interfering RNA and methyl-β-cyclodextrin (Mβ-CD) decreased galectin-1-induced
cyclin expression and [3H]-thymidine incorporation. Galectin-1 caused Akt and mTOR phosphorylation, which is involved in cyclin expression. Galectin-1-induced
phospho-Akt and -mTOR was inhibited by PP2, ERas siRNA, caveolin-1 siRNA and Mβ-CD. Furthermore, mTOR phosphorylation was
decreased by LY294002 and Akt inhibitor. Galectin-1-induced increase in cyclin expression and decrease in p27kip1 was blocked by Akt inhibitor and rapamycin. In conclusion, galectin-1 increased DNA synthesis in mouse ES cells via Src,
caveolin-1 Akt, and mTOR signaling pathways.
Received 30 October 2008; received after revision 18 February 2009; accepted 24 February 2009 相似文献
2.
3.
Hsu SP Ho PY Juan SH Liang YC Lee WS 《Cellular and molecular life sciences : CMLS》2008,65(23):3839-3850
Previous studies have shown that progesterone inhibits endothelial cell proliferation through a nuclear receptor-mediated
mechanism. Here, we further demonstrate that progesterone at physiologic levels (5 – 500 nM) dose- and time-dependently inhibited
DNA synthesis of cultured human umbilical vein endothelial cells (HUVEC). The mRNA and protein levels of p21, p27, and p53
in HUVEC were increased by progesterone. The formation of CDK2-p21 and CDK2-p27 were increased and the CDK2 activity was decreased
in the progesterone-treated HUVEC. The progesterone-inhibited [3H]thymidine incorporation was completely blocked when the
expressions of p21 and p27 were knocked-down together. Transfection of HUVEC with dominant negative p53 cDNA prevented the
progesterone-induced increases in p21 and p27 promoter activity and protein level, decreases in thymidine incorporation, and
capillary-like tube formation. Matrigel angiogenesis assay in mice demonstrated the antiangiogenic effect of progesterone
in vivo. These findings demonstrate for the first time that progesterone inhibited endothelial cell proliferation through a p53-dependent
pathway.
Received 28 July 2008; received after revision 25 September 2008; accepted 26 September 2008 相似文献
4.
C. L. Salanga M. O’Hayre T. Handel 《Cellular and molecular life sciences : CMLS》2009,66(8):1370-1386
Chemokines are small, secreted proteins that bind to the chemokine receptor subfamily of class A G protein-coupled receptors.
Collectively, these receptor-ligand pairs are responsible for diverse physiological responses including immune cell trafficking,
development and mitogenic signaling, both in the context of homeostasis and disease. However, chemokines and their receptors
are not isolated entities, but instead function in complex networks involving homo- and heterodimer formation as well as crosstalk
with other signaling complexes. Here the functional consequences of chemokine receptor activity, from the perspective of both
direct physical associations with other receptors and indirect crosstalk with orthogonal signaling pathways, are reviewed.
Modulation of chemokine receptor activity through these mechanisms has significant implications in physiological and pathological
processes, as well as drug discovery and drug efficacy. The integration of signals downstream of chemokine and other receptors
will be key to understanding how cells fine-tune their response to a variety of stimuli, including therapeutics.
Received 19 October 2008; received after revision 7 November 2008; accepted 11 November 2008
C. L. Salanga, M. O’Hayre: These authors contributed equally. 相似文献
5.
Here we examine differentiation of the intestinal cell line Caco-2 following exposure to sodium butyrate (NaBT), using alkaline phosphatase (ALP) activity and carcinoembryonic antigen (CEA) levels as markers of differentiation. We show that acetylcholinesterase (AChE) activity and RNA levels increase during differentiation. Treatment with AChE inhibitors or knockdown of AChE levels by shRNA markedly decrease ALP and CEA levels in a concentration- and time-dependent manner. Finally, our observations suggest that NaBT-induced differentiation of intestinal cells involves AChE-induced cell cycle arrest. 相似文献
6.
Stem cells are a powerful resource for cell-based transplantation therapies in osteodegenerative disorders, but before some kinds of stem cells can be applied clinically, several aspects of their expansion and differentiation need to be better controlled. Wnt molecules and members of the Wnt signaling cascade have been ascribed a role in both these processes in vitro as well as normal development in vivo. However some results are controversial. In this review we will present the hypothesis that both canonical and non-canonical signaling are involved in mesenchymal cell fate regulation, such as adipogenesis, chondrogenesis and osteogenesis, and that in vitro it is a timely switch between the two that specifies the identity of the differentiating cell. We will specifically focus on the in vitro differentiation of adipocytes, chondrocytes and osteoblasts contrasting embryonic and mesenchymal stem cells as well as the role of Wnts in mesenchymal fate specification during embryogenesis. 相似文献
7.
P. J. Lardone A. Carrillo-Vico P. Molinero A. Rubio J. M. Guerrero 《Cellular and molecular life sciences : CMLS》2009,66(3):516-525
Human lymphocyte melatonin, through membrane and nuclear receptors binding, acts as an activator in IL-2 production. Antagonism
of membrane melatonin receptors using luzindole exacerbates the drop of the IL-2 production induced by PGE2 in peripheral blood mononuclear and Jurkat cells. This paper studies the melatonin membrane and nuclear receptors interplay
in PGE2-diminished IL-2 production. The decrease in IL-2 production after PGE2 and/or luzindole administration correlated with downregulation in the nuclear receptor RORα. We also highlighted a role of
cAMP in the pathway, because forskolin mimicked the effects of luzindole and/or PGE2 in the RORα expression. Finally, a significant RORα downregulation was observed in T cells permanently transfected with inducible
MT1 antisense. In conclusion, we show a novel connection between melatonin membrane receptor signalling and RORα expression,
opening a new way to understand melatonin regulation in lymphocyte physiology.
Received 23 September 2008; received after revision 19 November 2008; accepted 21 November 2008 相似文献
8.
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
9.
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
10.
Mitochondrial dysfunction and protein kinase C (PKC) activation are consistently found in diabetic cardiomyopathy but their
relationship remains unclear. This study identified mitochondrial aconitase as a downstream target of PKC activation using
immunoblotting and mass spectrometry, and then characterized phosphorylation-induced changes in its activity in hearts from
type 1 diabetic rats. PKCβ2 co-immunoprecipitated with phosphorylated aconitase from mitochondria isolated from diabetic hearts. Augmented phosphorylation
of mitochondrial aconitase in diabetic hearts was found to be associated with an increase in its reverse activity (isocitrate
to aconitate), while the rate of the forward activity was unchanged. Similar results were obtained on phosphorylation of mitochondrial
aconitase by PKCβ2 in vitro. These results demonstrate the regulation of mitochondrial aconitase activity by PKC-dependent phosphorylation. This may
influence the activity of the tricarboxylic acid cycle, and contribute to impaired mitochondrial function and energy metabolism
in diabetic hearts.
Received 31 October 2008; received after revision 17 December 2008; accepted 2 January 2009 相似文献
11.
T. Mueller J. Luetzkendorf K. Nerger H.-J. Schmoll L. P. Mueller 《Cellular and molecular life sciences : CMLS》2009,66(3):495-503
OCT4 is considered a main regulator of embryonic stem cell pluripotency and self renewal capacity. It was shown that relevant
OCT4 expression only occurs in cells of embryonic pluripotent nature. However, several recent publications claimed to have
demonstrated OCT4 expression in human somatic tumor cells, human adult stem or progenitor cells and differentiated cells.We
analysed 42 human tumor cell lines from 13 entities and human bone marrowderived mesenchymal stem cells (MSC). To validate
OCT4 expression we used germ cell tumor (GCT) cell lines, derived xenografts and GCT samples. Analysis by RT-PCR, western
blotting, immunocytochemistry and immunohistochemistry was performed. With exception of typical embryonal carcinoma cells,
we did not observe reliable OCT4 expression in somatic tumor cell lines and MSC. We suggest that a high level of expression
of the OCT4 protein together with its nuclear localization still remains a reliable and definitive feature of cells with embryonic
pluripotent nature.
Received 30 September 2008; received after revision 05 November 2008; accepted 10 November 2008 相似文献
12.
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
13.
K. L. Sand E. Knudsen J. Rolin Y. Al-Falahi A. A. Maghazachi 《Cellular and molecular life sciences : CMLS》2009,66(8):1446-1456
Glatiramer acetate (GA or Copaxone) is a drug used to treat experimental autoimmune encephalomyelitis in mice and multiple
sclerosis in human. Here, we describe a new mechanism of action for this drug. GA enhanced the cytolysis of human NK cells
against autologous and allogeneic immature and mature monocyte-derived dendritic cells (DCs). This drug reduced the percentages
of mature DCs expressing CD80, CD83, HLA-DR or HLA-I. In contrast, it did not modulate the percentages of NK cells expressing
NKG2D, NKp30, or NKp44. Nonetheless, anti-NKp30 or anti-CD86 inhibited GA-enhanced human NK cell lysis of immature DCs. Hence,
CD86, and NKp30 are important for NK cell lysis of immature DCs, whereas CD80, CD83, HLA-DR and HLA-I are important for the
lysis of mature DCs when GA is used as a stimulus. Further, GA inhibited the release of IFN-γ 24 h but increased the release
of TNF-α 48 h after incubation with NK cells.
Received 13 November 2008; received after revision 10 February 2009; accepted 18 February 2009 相似文献
14.
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
15.
K. Mutyambizi C. L. Berger R. L. Edelson 《Cellular and molecular life sciences : CMLS》2009,66(5):831-840
Langerhans cells are immature skin-homing dendritic cells that furnish the epidermis with an immune surveillance system, and
translate information between the internal and external milieu. Dendritic cells, in particular Langerhans cells, are gaining
prominence as one of the potential principal players orchestrating the decision between immunity and tolerance. Langerhans
cells capture aberrant self-antigen and pathogen-derived antigen for display to the efferent immune response. Recent evidence
suggests redundancy in the antigen-presenting function of Langerhans cells, with dermal dendritic subsets capable of fulfilling
an analogous role. There is mounting evidence that Langerhans cells can cross-prime T cells to recognize antigens. Langerhans
cells are proposed to stimulate T regulatory cells, and are implicated in the pathogenesis of cutaneous T cell lymphoma.The
phenotype of Langerhans cells, which may be tolerogenic or immunogenic, appears to depend on their state of maturity, inciting
immunogen and cytokine environment, offering the potential for manipulation in immunotherapy.
Received 6 August 2008; received after revision 18 September 2008; accepted 13 October 2008 相似文献
16.
C.-J. Chang P.-H. Yin D.-M. Yang C.-H. Wang W.-Y. Hung C.-W. Chi Y.-H. Wei H.-C. Lee 《Cellular and molecular life sciences : CMLS》2009,66(10):1755-1765
The aim of this study was to investigate the contribution of mitochondrial dysfunction to chemoresistance and migration of
hepatoma cells. We found that inhibition of mitochondrial respiration and mitochondrial DNA (mtDNA) depletion resulted in
induction of amphiregulin (AR) expression in HepG2 cells. Upon oligomycin treatment of HepG2 cells, the cytosolic Ca2+ was significantly raised after 30 min, and the intracellular level of reactive oxygen species (ROS) was elevated 2.2-fold
after 4 h. Moreover, the condition medium of oligomycin-treated HepG2 cells was found to stimulate the migration of SK-Hep-1
cells. On the other hand, oligomycin-induced cisplatin-resistance and cell migration of HepG2 cells were attenuated by AR-specific
RNA interference (#L-017435, Dharmacon) and a neutralizing antibody (MAB262, R&D Systems), respectively. Together, these findings
suggest that mitochondrial dysfunction induced Ca2+ mobilization, and ROS overproduction, which modulated the chemo-resistance and migration of hepatoma cells through the induction
and activation of AR.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.
Y.-H. Wei, H.-C. Lee: These authors contribute equally to this work.
Received 02 December 2008; received after revision 16 March 2009; accepted 17 March 2009 相似文献
17.
18.
The multifunctional roles of the four-and-a-half-LIM only protein FHL2 总被引:14,自引:1,他引:14
Johannessen M Møller S Hansen T Moens U Van Ghelue M 《Cellular and molecular life sciences : CMLS》2006,63(3):268-284
19.
Protein kinase C (PKC) is an important signaling molecule in the heart, but its targets remain unclear. Using a PKC substrate
antibody, we detected a 40-kDa phosphorylated cardiac protein that was subsequently identified by tandem mass spectroscopy
as muscle creatine kinase (M-CK) with phosphorylation at serine 128. The forward reaction using ATP to generate phosphocreatine
was reduced, while the reverse reaction using phosphocreatine to generate ATP was increased following dephosphorylation of
immunoprecipitated M-CK with protein phosphatase 2A (PP2A) or PP2C. Despite higher PKC levels in diabetic hearts, decreased
phosphorylation of M-CK was more prominent than the reduction in its expression. Changes in CK activity in diabetic hearts
were similar to those found following dephosphorylation of M-CK from control hearts. The decrease in phosphorylation may act
as a compensatory mechanism to maintain CK activity at an appropriate level for cytosolic ATP regeneration in the diabetic
heart.
Received 15 September 2008; received after revision 30 September 2008; accepted 13 October 2008 相似文献