共查询到20条相似文献,搜索用时 31 毫秒
1.
Doerwald L van Genesen ST Onnekink C Marín-Vinader L de Lange F de Jong WW Lubsen NH 《Cellular and molecular life sciences : CMLS》2006,63(6):735-743
The mechanism of the translational thermotolerance provided by the small heat shock proteins (sHsps) αB-crystallin or Hsp27
is unknown. We show here that Hsp27, but not αB-crystallin, increased the pool of mobile stress granule-associated enhanced
green fluorescent protein (EGFP)-eukaryotic translation initiation factor (eIF)4E in heat-shocked cells, as determined by
fluorescence recovery after photobleaching. Hsp27 also partially prevented the sharp decrease in the pool of mobile cytoplasmic
EGFP-eIF4G. sHsps did not prevent the phosphorylation of eIF2α by a heat shock, but promoted dephosphorylation during recovery.
Expression of the C-terminal fragment of GADD34, which causes constitutive dephosphorylation of eIF2α, fully compensated for
the stimulatory effect of αB-crystallin on protein synthesis in heat-shocked cells, but only partially for that of Hsp27.
Our data show that sHsps do not prevent the inhibition of protein synthesis upon heat shock, but restore translation more
rapidly by promoting the dephosphorylation of eIF2α and, in the case of Hsp27, the availability of eIF4E and eIF4G.
Received 9 December 2005; received after revision 16 January 2006; accepted 23 January 2006 相似文献
2.
Parihar MS Parihar A Fujita M Hashimoto M Ghafourifar P 《Cellular and molecular life sciences : CMLS》2008,65(7-8):1272-1284
α-Synuclein is a neuron-specific protein that contributes to the pathology of Parkinson’s disease via mitochondria-related mechanisms. The present study investigated possible interaction of α-synuclein with mitochondria and
consequences of such interaction. Using SHSY cells overexpressing α-synuclein A53T mutant or wild-type, as well as isolated
rat brain mitochondria, the present study shows that α-synuclein localizes at the mitochondrial membrane. In both SHSY cells
and isolated mitochondria, interaction of α-synuclein with mitochondria causes release of cytochrome c, increase of mitochondrial calcium and nitric oxide, and oxidative modification of mitochondrial components. These findings
suggest a pivotal role for mitochondria in oxidative stress and apoptosis induced by α-synuclein.
Received 27 December 2007; received after revision 7 February 2008; accepted 8 February 2008 相似文献
3.
E. Cohen-Hillel R. Mintz T. Meshel B.-Z. Garty A. Ben-Baruch 《Cellular and molecular life sciences : CMLS》2009,66(5):884-899
The chemokine CXCL8 is a powerful inducer of directional cell motility, primarily during inflammation. In this study, we found
that CXCL8 stimulation led to paxillin phosphorylation in normal neutrophils, and that both CXCL8 receptors (CXCR1 and CXCR2)
mediated CXCL8-induced paxillin phosphorylation. In CXCR2-transfected cells, the process depended on Gαi and Gαs coupling to CXCR2. Dominant negative (DN) paxillin increased CXCL8-induced adhesion and migration, indicating that endogenous
paxillin keeps migration at submaximal levels. Furthermore, using activating antibodies to β1 integrins, analyses with focal
adhesion kinase (FAK) DN variant (FRNK) and co-immunoprecipitations of FAK and paxillin, we found that β1 integrin ligation
cooperates with CXCL8-induced stimulation, leading to FAK activation and thereafter to FAK-mediated paxillin phosphorylation.
Our findings indicate that paxillin keeps directional motility at a restrained magnitude, and suggest that perturbations in
its activation may lead to chemotactic imbalance and to pathological conditions associated with excessive or reduced leukocyte
migration.
R. Mintz, T. Meshel: These authors contributed equally to this work.
Received 31 July 2008; received after revision 14 December 2008; accepted 16 December 2008 相似文献
4.
B. Schäfer C. Götz J. Dudek A. Hessenauer U. Matti M. Montenarh 《Cellular and molecular life sciences : CMLS》2009,66(2):339-349
Protein kinase CK2 is a highly conserved serine/threonine kinase that is ubiquitously expressed in eukaryotic cells. CK2 is
a constitutively active tetrameric enzyme composed of two catalytic α and/or α’-subunits and two regulatory β-subunits. There
is increasing evidence that the individual subunits may have independent functions and that they are asymmetrically distributed
inside the cell. To gain a better understanding of the functions of the individual subunits, we employed a yeast-two-hybrid
screen with CK2α and CK2α’. We identified the motor neuron protein KIF5C as a new binding partner for CK2. The interaction
found in the yeast-two-hybrid screen was confirmed by co-sedimentation analysis on a sucrose density gradient and by co-immunoprecipitation
analysis. Pull-down experiments and surface plasmon resonance spectrometry revealed a direct binding of KIF5C to CK2α’. Co-localization
studies with neuroblastoma cells, bone marrow and with primary neurons confirmed the biochemical analysis that KIF5C preferentially
bound to CK2α’.
Received 8 August 2008; received after revision 3 November 2008; accepted 4 November 2008 相似文献
5.
AMP-activated protein kinase in skeletal muscle: From structure and localization to its role as a master regulator of cellular metabolism 总被引:1,自引:0,他引:1
Witczak CA Sharoff CG Goodyear LJ 《Cellular and molecular life sciences : CMLS》2008,65(23):3737-3755
The AMP-activated protein kinase (AMPK) is a metabolite sensing serine/threonine kinase that has been termed the master regulator
of cellular energy metabolism due to its numerous roles in the regulation of glucose, lipid, and protein metabolism. In this
review, we first summarize the current literature on a number of important aspects of AMPK in skeletal muscle. These include
the following: (1) the structural components of the three AMPK subunits (i.e. AMPKα, β, and γ), and their differential localization
in response to stimulation in muscle; (2) the biochemical regulation of AMPK by AMP, protein phosphatases, and its three known
upstream kinases, LKB1, Ca2+/calmodulin-dependent protein kinase kinase (CaMKK), and transforming growth factor-β-activated kinase 1 (TAK1); (3) the pharmacological
agents that are currently available for the activation and inhibition of AMPK; (4) the physiological stimuli that activate
AMPK in muscle; and (5) the metabolic processes that AMPK regulates in skeletal muscle.
Received 04 May 2008; received after revision 14 June 2008; accepted 14 July 2008 相似文献
6.
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
7.
In renal carcinoma cells (RCC4) hypoxia inducible factor-1 (HIF-1) is constitutively expressed due to a von Hippel Lindau
protein deficiency, but can be degraded by calpain, independently of the 26S proteasome, when exposed to hypoxia/nitric oxide
(NO). In this study we examined molecular mechanisms to explain calpain activation. The inability of hypoxia/NO to degrade
HIF-1α in respiratory-deficient RCC4-ρ0 cells pointed to the requirement for mitochondria-derived reactive oxygen species.
A prerequisite for O
2
−
in combination with NO to destabilize HIF-1α was corroborated in RCC4-p0 cells, when the redox cycler 2,3-dimethoxy-1,4-naphthoquinone
was used as a source of superoxide. Degradation of HIF-1α required intracellular calcium transients and calpain activation.
Using uric acid to interfere with signal transmission elicited by NO/O
2
−
blocked HIF-1α degradation and attenuated a calcium increase. We conclude that an oxidative signal as a result of NO/O
2
−
coformation triggers a calcium increase that activates calpain to degrade HIF-1α, independently of the proteasome.
Received 14 August 2007; received after revision 4 October 2007; accepted 22 October 2007 相似文献
8.
9.
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
10.
Tang J Wu YM Zhao P Yang XM Jiang JL Chen ZN 《Cellular and molecular life sciences : CMLS》2008,65(18):2933-2942
Mechanism of HAb18G/CD147 underlying the metastasis process of human hepatoma cells has not been determined. In the present
study, we found that integrin α3β1 colocalizes with HAb18G/CD147 in human 7721 hepatoma cells. The enhancing effect of HAb18G/CD147
on adhesion, invasion capacities and matrix metalloproteinases (MMPs) secretion was decreased by integrin α3β1 antibodies
(p<0.01). The expressions of integrin downstream molecules including focal adhesion kinase (FAK), phospho-FAK (p-FAK), paxillin,
and phospho-paxillin (p-paxillin) were increased in human hepatoma cells overexpressing HAb18G/CD147. Deletion of HAb18G/CD147
reduces the quantity of focal adhesions and rearranges cytoskeleton. Wortmannin and LY294002, specific phosphatidylinositol
kinase (PI3K) inhibitors, reversed the effect of HAb18G/CD147 on the regulation of intracellular Ca2+ mobilization, significantly reducing cell adhesion, invasion and MMPs secretion potential (p<0.01). Together, these results suggest that HAb18G/CD147 enhances the invasion and metastatic potentials of human hepatoma
cells via integrin α3β1-mediated FAK-paxillin and FAKPI3K-Ca2+ signal pathways.
Received 5 June 2008; received after revision 16 July 2008; accepted 23 July 2008 相似文献
11.
Nabeshima Y 《Cellular and molecular life sciences : CMLS》2008,65(20):3218-3230
The traditional view of calcium homeostasis is that it is maintained by two essential reactions. First, changes in extracellular
Ca2+ are sensed in several distinct cell types, stimulating the secretion of parathyroid hormone (PTH), 1,25(OH)2 D and calcitonin in response to the body’s requirement. Second, these calcitropic hormones then act on the calcium-translocating
cells of the kidney, bone, and intestine to restore calcium balance. Recent progress indicates that α-Klotho and fibroblast
growth factor (FGF) 23 are key players that integrate the multi-step regulatory system of calcium homeostasis that rapidly
adjusts the extracellular calcium concentration and continuously maintains its concentration within a narrow physiological
range. α-Klotho and FGF23 are also found to be major players in the regulatory system of phosphate homeostasis. Here, the
demonstration of the molecular functions of α-Klotho and FGF23 has recently given new insight into the field of calcium and
phosphate homeostasis.
Received 3 April 2008; received after revision 23 May 2008; accepted 5 June 2008 相似文献
12.
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
13.
N. Obermajer Z. Jevnikar B. Doljak A. M. Sadaghiani M. Bogyo J. Kos 《Cellular and molecular life sciences : CMLS》2009,66(6):1126-1134
Membrane nanotubes were recently described as a new principle of cell–cell communication enabling complex and specific messaging
to distant cells. Calcium fluxes, vesicles, and cell-surface components can all traffic between cells connected by nanotubes.
Here we report for the first time the mechanism of membrane nanotube formation in T cells through LFA-1 (CD11a/CD18; αLβ2) integrin activation by the cysteine protease cathepsin X. Cathepsin X is shown to induce persistent LFA-1 activation. Cathepsin
X-upregulated T cells exhibit increased homotypic aggregation and polarized, migration-associated morphology in 2D and 3D
models, respectively. In these cells, extended uropods are frequently formed, which subsequently elongate to nanotubes connecting
T lymphocytes. Our results demonstrate that LFA-1 activation with subsequent cytoskeletal reorganization induces signal transmission
through a physically connected network of T lymphocytes for better coordination of their action at various stages of the immune
response.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.
Received 26 December 2008; received after revision 26 January 2009; accepted 27 January 2009
N. Obermajer, Z. Jevnikar: These authors contributed equally to the present work. 相似文献
14.
Sanchez-Perez I Rodriguez-Hernandez CJ Manguan-García C Torres A Perona R Murguía JR 《Cellular and molecular life sciences : CMLS》2004,61(6):700-708
The immunosuppressants tacrolimus (FK506) and cyclosporin A (CsA) have increased the survival rates in organ transplantation. Both drugs inhibit the protein phosphatase calcineurin (CaN) in activated T cells, exhibiting similar side-effects. Diabetes is observed more often in FK506 than CsA therapy, probably due to inhibition of new molecular targets other than CaN. We studied FK506 toxicity in mammalian cells. FK506, but not CsA, regulated p38 activation by osmotic stress, and decreased viability in osmostressed cells. In addition, FK506 treatment strongly increased the phosphorylation of the eukaryotic initiation factor-2a (eIF-2a) subunit. eIF-2a phosphorylation, p38 inhibition and cell lethality were relieved by addition of excess amino acids to the medium, suggesting that amino acid availability mediated FK506 toxicity. Therefore, these FK506-dependent responses could be relevant to the non-therapeutic effects of FK506 therapy.Received 16 October 2003; received after revision 8 January 2004; accepted 14 January 2004 相似文献
15.
A. Hamadi T. B. Deramaudt K. Takeda P. Rondé 《Cellular and molecular life sciences : CMLS》2009,66(2):324-338
Cell migration requires the coordinated turnover of focal adhesions, a process that involves FAK phosphorylation. Since Src
is the major kinase implicated in FAK phosphorylation, we focus here on the role of Src activation on adhesion remodelling.
In astrocytoma cells, constitutively activated Src induces both FAK phosphorylation and adhesion rearrangement. To evaluate
how Src controls these processes, we used a recently described Src reporter to monitor the dynamics of Src phosphorylation.
Upon Src activation, focal adhesions started to disassemble while Src appeared highly expressed at newly formed membrane ruffles.
Kinetic analysis of time-lapse movies showed that loss of phospho-Src at focal adhesions was time-correlated with the appearance
of membrane ruffles containing phospho-Src. Moreover, FLIP analysis revealed a dynamic equilibrium of Src between focal adhesions
and membrane ruffles. We conclude that upon phosphorylation, Src is directly translocated from focal adhesions to membrane
ruffles, thereby promoting formation of new adhesion complexes.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.
Received 21 July 2008; received after revision 10 October 2008; accepted 03 November 2008 相似文献
16.
Zaitseva II Størling J Mandrup-Poulsen T Berggren PO Zaitsev SV 《Cellular and molecular life sciences : CMLS》2008,65(7-8):1248-1255
An insufficient number of insulin-producing β-cells is a major cause of defective control of blood glucose in both type 1
and type 2 diabetes. The aim of this study was to clarify whether the insulinotropic imidazolines can affect the survival
of highly proliferating insulin-secreting cells, here exemplified by the MIN6 cell line. Our data demonstrate that RX871024,
but not efaroxan, triggered MIN6 cell death and potentiated death induced by a combination of the pro-inflammatory cytokines
interleukin-1β, interferon- γ and tumor necrosis factor-α. These effects did not involve changes in nitric oxide production
but correlated with stimulation of c-jun N-terminal kinase (JNK) activity and activation of caspases-1, -3, -8 and -9. Our
results suggest that the imidazoline RX871024 causes death of highly proliferating insulin-secreting cells, putatively via augmentation of JNK activity, a finding that may impact on the possibility of using compounds of similar activity in the
treatment of diabetes.
Received 13 December 2007; received after revision 5 February 2008; accepted 6 February 2008 相似文献
17.
Recent work in the α thalassaemia field has started to provide some indication of the mechanisms involved in the very high
frequency of the different forms of α thalassaemia among the populations of tropical countries, and, at the same time, is
starting to define at least some of the mechanisms for its remarkable phenotypic heterogeneity. These diseases continue to
provide extremely valuable models for the better understanding of the regulation of the α globin genes, and for human molecular
pathology in general. The much less common disorders, ATR-16 and ATR-X are also providing valuable information about the spectrum
of molecular lesions associated with different forms of mental retardation and about the molecular mechanisms involved in
their varying phenotypes.
Received 29 August 2008; received after revision 07 October 2008; accepted 14 October 2008 相似文献
18.
R. J. S. Viana A. F. Nunes R. E. Castro R. M. Ramalho J. Meyerson S. Fossati J. Ghiso A. Rostagno C. M. P. Rodrigues 《Cellular and molecular life sciences : CMLS》2009,66(6):1094-1104
The vasculotropic E22Q mutant of the amyloid-β (Aβ) peptide is associated with hereditary cerebral hemorrhage with amyloidosis
Dutch type. The cellular mechanism(s) of toxicity and nature of the AβE22Q toxic assemblies are not completely understood.
Comparative assessment of structural parameters and cell death mechanisms elicited in primary human cerebral endothelial cells
by AβE22Q and wild-type Aβ revealed that only AβE22Q triggered the Bax mitochondrial pathway of apoptosis. AβE22Q neither
matched the fast oligomerization kinetics of Aβ42 nor reached its predominant β-sheet structure, achieving a modest degree
of oligomerization with a secondary structure that remained a mixture of β and random conformations. The endogenous molecule
tauroursodeoxycholic acid (TUDCA) was a strong modulator of AβE22Q-triggered apoptosis but did not significantly change the
secondary structures and fibrillogenic propensities of Aβ peptides. These data dissociate the pro-apoptotic properties of
Aβ peptides from their distinct mechanisms of aggregation/fibrillization in vitro, providing new perspectives for modulation of amyloid toxicity.
Received 20 November 2008; received after revision 12 December 2008; accepted 12 January 2009 相似文献
19.
Sniekers M Foulon V Mannaerts GP Van Maldergem L Mandel H Gelb BD Casteels M Van Veldhoven PP 《Cellular and molecular life sciences : CMLS》2006,63(13):1553-1563
The identification of 2-hydroxyphytanoyl-CoA lyase (2-HPCL), a thiamine pyrophosphate (TPP)-dependent peroxisomal enzyme involved
in the α-oxidation of phytanic acid and of 2-hydroxy straight chain fatty acids, pointed towards a role of TPP in these processes.
Until then, TPP had not been implicated in mammalian peroxisomal metabolism. The effect of thiamine deficiency on 2-HPCL and
α-oxidation has not been studied, nor have possible adverse effects of deficient α-oxidation been considered in the pathogenesis
of diseases associated with thiamine shortage, such as thiamine-responsive megaloblastic anemia (TRMA). Experiments with cultured
cells and animal models showed that α-oxidation is controlled by the thiamine status of the cell/tissue/organism, and suggested
that some pathological consequences of thiamine starvation could be related to impaired α-oxidation. Whereas accumulation
of phytanic acid and/or 2-hydroxyfatty acids or their α-oxidation intermediates in TRMA patients given a normal supply of
thiamine is unlikely, this may not be true when malnourished.
Received 23 December 2005; received after revision 10 April 2006; accepted 28 April 2006 相似文献