共查询到20条相似文献,搜索用时 763 毫秒
1.
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
2.
Diego-García E Abdel-Mottaleb Y Schwartz EF de la Vega RC Tytgat J Possani LD 《Cellular and molecular life sciences : CMLS》2008,65(1):187-200
Among the scorpion venom components whose function are poorly known or even show contrasting pharmacological results are those
called “orphan peptides”. The most widely distributed are named β-KTx or scorpine-like peptides. They contain three disulfide
bridges with two recognizable domains: a freely moving N-terminal amino acid sequence and a tightly folded C-terminal region
with a cysteine-stabilized α/β (CS-αβ) motif. Four such peptides and three cloned genes are reported here. They were assayed
for their cytolytic, antimicrobial and K
+ channel-blocking activities. Two main characteristics were found: the existence of an unusual structural and functional diversity,
whereby the full-length peptide can lyse cells or kill microorganisms, and a C-terminal domain containing the CS-αβ motif
that can block K
+ channels. Furthermore, sequence analyses and phylogenetic reconstructions are used to discuss the evolution of this type
of peptide and to highlight the versatility of the CS-αβ structures.
Received 13 August 2007; received after revision 30 October 2007; accepted 2 November 2007 相似文献
3.
Martínez-Salgado C Rodríguez-Peña AB López-Novoa JM 《Cellular and molecular life sciences : CMLS》2008,65(3):477-492
The mechanisms involved in the development of renal fibrosis are poorly understood. Small Ras GTPases control cell proliferation,
differentiation, cellular growth and apoptosis, with cell-specific expression in the kidney. Cytokines, high glucose medium
or advanced glycation end-products activate Ras in different renal cells. Increased Ras activation has been found in experimental
tubulointerstitial fibrosis. Transforming growth factor-β1 (TGF-β1) and Ras signalling pathways are close related: TGF-β1
overcomes Ras mitogenic effects, and Ras counteracts TGF-β signalling. However, Ras activation is also an intracellular signal
transduction point for several molecules (e.g. TGF-β1) involved in kidney damage. Ras isoforms play different roles in regulating extracellular matrix synthesis in fibroblasts
and mesangial cells. These data give evidence for a role for Ras in renal fibrosis, but no reviews are available on the role
of p21 Ras in this process. Thus, our goal is to review the role of Ras activation and signalling in renal fibrosis.
Received 7 June 2007; received after revision 17 September 2007; accepted 1 October 2007 相似文献
4.
Cheema U Brown RA Alp B MacRobert AJ 《Cellular and molecular life sciences : CMLS》2008,65(1):177-186
Tissue hypoxia results in rapid angiogenesis in vivo, triggered by angiogenic proteins, including vascular endothelial growth factor (VEGF). Current views of tissue viability
are founded on whether ‘deeper-lying’ cells receive sufficient nutrients and oxygen for normal activity and ultimately survival.
For intact tissues, levels of such essential nutrients are governed by micro-vascular perfusion. However, there have been
few effective quantitatively defined 3D models, which enable testing of the interplay or interdependence of matrix and cell
density, and path diffusion on oxygen consumption in vitro. As a result, concepts on cell vulnerability to low oxygen levels, together with the nature of cellular responses are ill
defined. The present study has adapted a novel, optical fibre-based system for in situ, real-time oxygen monitoring within three-dimensionally-spiralled cellular collagen constructs, which were then unfurled
to enable quantitative, spatial measurements of VEGF production in different parts of the same construct exposed to different
oxygen levels. A VEGF response was elicited by cells exposed to low oxygen levels (20 mmHg), primarily within the construct
core.
Received 3 August 2007; received after revision 24 October 2007; accepted 29 October 2007
An erratum to this article is available at . 相似文献
5.
Viero G Gropuzzo A Joubert O Keller D Prévost G Dalla Serra M 《Cellular and molecular life sciences : CMLS》2008,65(2):312-323
γ-Hemolysins are pore-forming toxins which develop from water-soluble monomers by combining two different ‘albeit homologous’
proteins. They form oligomeric pores in both cell and model membranes by undergoing a still poorly understood conformational
rearrangement in the stem region. The stem is formed by three β-strands, folded onto the core of the soluble protein and completely
extended in the pore. We propose a new model to explain such a process. Seven double-cysteine mutants were developed by inserting
one cysteine on the stretch that links the β-hairpin to the core of the protein and another on different positions along the
β-strands. The membrane bound protein was blocked in a non-lytic state by S–S bond formation. Six mutants were oxidized as
inactive intermediates, but became active after adding DTT. These results demonstrate that the stem extension can be temporarily
frozen and that the β-barrel formation occurs by β-strand concerted step-by-step sliding.
Received 22 October 2007; received after revision 15 November 2007; accepted 19 November 2007 相似文献
6.
Suzuki Y 《Cellular and molecular life sciences : CMLS》2008,65(3):351-353
We have proposed a chemical chaperone therapy for lysosomal diseases, based on a paradoxical phenomenon that an exogenous
competitive inhibitor of low molecular weight stabilizes the target mutant molecule and restores its catalytic activity as
a molecular chaperone intracellularly. After Fabry disease experiments, we investigated a new synthetic chaperone compound
N-octyl-4-epi-β-valienamine (NOEV) in a GM1-gangliosidosis model mice. Orally administered NOEV entered the brain through the blood-brain barrier, enhanced β-galactosidase
activity, reduced the substrate storage, and clinically improved neurological deterioration. We hope that chemical chaperone
therapy will prove useful for some patients with GM1-gangliosidosis and potentially other lysosomal storage diseases with central nervous system involvement.
Received 10 October 2007; received after revision 31 October 2007; accepted 6 November 2007 相似文献
7.
Prosperi-Meys C Wouters J Galleni M Lamotte-Brasseur J 《Cellular and molecular life sciences : CMLS》2001,58(14):2136-2143
Increased resistance to β-lactam antibiotics is mainly due to β-lactamases whose production by pathogenic bacteria makes their broad activity spectrum
especially frightening. X-ray structures of several zinc β-lactamases have revealed the coordination of the two metal ions, but their mode of action remains unclear. Geometry optimisation
of stable complexes along the reaction pathway of benzylpenicillin hydrolysis highlighted a proton shuttle occurring from
D120 of the Bacillus cereus β-lactamase to the β-lactam nitrogen via Zn2 which is central to the network. First, the Zn1 ion has a structural role maintaining Zn-bound waters,
WAT1 and WAT2, either directly or through the Zn1 tetrahedrally coordinated histidine ligands. The Zn2 ion has a more catalytic
role, stabilising the tetrahedral intermediate, accepting the β-lactam nitrogen atom as a ligand. The role of Zn2 and the flexibility in the coordination geometry of both Zn ions is of
crucial importance for catalysis.
Received 14 August 2001; received after revision 19 October 2001; accepted 30 October 2001 相似文献
8.
Cell adhesion molecules (CAMs) have been implicated in the control of a wide variety of cellular processes, such as cell adhesion,
polarization, survival, movement, and proliferation. Nectins have emerged as immunoglobulin-like CAMs that participate in
calcium-independent cell-cell adhesion by homophilic and heterophilic trans-interactions with nectins and nectin-like molecules. Nectin-based cell-cell adhesion exerts its function independently or
in cooperation with other CAMs including cadherins and is essential for the formation of intercellular junctions, including
adherens junctions, tight junctions, and puncta adherentia junctions. Nectins cis-interact with integrin αvβ3 and platelet-derived growth factor receptor and facilitate their signals to regulate the formation and integrity of intercellular
junctions and cell survival. Nectins intracellularly associate with peripheral membrane proteins, including afadin and Par-3.
This review focuses on recent progress in understanding the interactions of nectins with other transmembrane and peripheral
membrane proteins to exert pleiotropic functions.
Received 27 June 2007; received after revision 14 August 2007; accepted 12 September 2007 相似文献
9.
Hyaluronan synthesis and degradation in cartilage and bone 总被引:1,自引:0,他引:1
Bastow ER Byers S Golub SB Clarkin CE Pitsillides AA Fosang AJ 《Cellular and molecular life sciences : CMLS》2008,65(3):395-413
Hyaluronan (HA) is a large but simple glycosaminoglycan composed of repeating D-glucuronic acid, β1–3 linked to N-acetyl-D-glucosamine β1–4, found in body fluids and tissues, in both intra- and extracellular compartments. Despite its structural
simplicity, HA has diverse functions in skeletal biology. In development, HA-rich matrices facilitate migration and condensation
of mesenchymal cells, and HA participates in joint cavity formation and longitudinal bone growth. In adult cartilage, HA binding
to aggrecan immobilises aggrecan, retaining it at the high concentrations required for compressive resilience. HA also appears
to regulate bone remodelling by controlling osteoclast, osteoblast and osteocyte behaviour. The functions of HA depend on
its intrinsic properties, which in turn rely on the degree of polymerisation by HA synthases, depolymerisation by hyaluronidases,
and interactions with HA-binding proteins. HA synthesis and degradation are closely regulated in skeletal tissues and aberrant
synthetic or degradative activity causes disease. The role and regulation of HA synthesis and degradation in cartilage, bone
and skeletal development is discussed.
Received 5 August 2007; received after revision 19 September 2007; accepted 20 September 2007 相似文献
10.
Nitric oxide plays a crucial role in cardiovascular homeostasis, with important vasodilatory, anti-thrombotic and anti-atherogenic
properties. β-Adrenergic receptors (βARs), present on a wide variety of cardiovascular cells, including vascular endothelial
cells, platelets, cardiac myocytes and leukocytes, have long been established as key players in maintaining cardiovascular
homeostatic control. During the last few years a wealth of evidence has emerged which directly links stimulation of these
cardiovascular βARs to nitric oxide (NO) generation, suggesting a new and important mechanism of adrenergic control of cardiovascular
function. This review explores the cardiovascular cell systems in which this coupling of βARs and NO occurs, the intracellular
signalling and regulatory mechanisms involved and the abnormalities in βAR-NO oxide coupling found in cardiovascular disease
states.
Received 30 September 2005; received after revision 24 November 2005; accepted 24 January 2006 相似文献
11.
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
12.
Leukocyte integrins and inflammation 总被引:6,自引:0,他引:6
C. G. Gahmberg L. Valmu S. Fagerholm P. Kotovuori E. Ihanus L. Tian T. Pessa-Morikawa 《Cellular and molecular life sciences : CMLS》1998,54(6):549-555
Leukocyte adhesion is of pivotal functional importance. Without adequate adhesion, T lymphocytes and natural killer cells
are not cytotoxic, B cells cannot develop into antibody secreting plasma cells, leukocytes do not home into inflamed tissues
and myeloid cells are not able to phagocytize or exhibit chemotactic responses. During evolution several leukocyte adhesion
molecules have developed belonging to a few molecular families. Among these, the leukocyte-specific integrins (β
2 integrins, CD11/CD18 molecules) are among the most important. Much progress has taken place during the past few years, and
at present we have a considerable knowledge of their structure and function. Inflammation is critically dependent on integrin
activity, and its regulation forms the topic of this short review. 相似文献
13.
Dassen H Punyadeera C Kamps R Klomp J Dunselman G Dijcks F de Goeij A Ederveen A Groothuis P 《Cellular and molecular life sciences : CMLS》2007,64(7-8):1009-1032
Genomic profiling was performed on explants of late proliferative phase human endometrium after 24-h treatment with progesterone
(P) or oestradiol and progesterone (17β-E2+P) and on explants of menstrual phase endometrium treated with 17β-E2+P. Gene expression was validated with real-time PCR in the samples used for the arrays, in endometrium collected from early
and mid-secretory phase endometrium, and in additional experiments performed on new samples collected in the menstrual and
late proliferative phase. The results show that late proliferative phase human endometrium is more responsive to progestins
than menstrual phase endometrium, that the expression of several genes associated with embryo implantation (i.e. thrombomodulin, monoamine oxidase A, SPARC-like 1) can be induced by P in vitro, and that genes that are fully dependent on the continuous presence of 17β-E2 during P exposure can be distinguished from those that are P-dependent to a lesser extent. Therefore, 17β-E2 selectively primes implantation-related genes for the effects of P.
H. Dassen, C. Punyadeera: These authors contributed equally.
Received 18 December 2006; received after revision 6 February 2007; accepted 8 March 2007 相似文献
14.
The rapid migration of intestinal epithelial cells (IEC) is important for the healing of mucosal wounds. We have previously
shown that polyamine depletion inhibits migration of IEC-6 cells. Akt activation and its downstream target GSK-3β have been
implicated in the regulation of migration. Here we investigated the significance of elevated phosphatidylinositol 3-kinase
(PI3K)/Akt signaling on migration of polyamine-depleted cells. Polyamine-depleted cells had high Akt (Ser473) and GSK-3β (Ser9)
phosphorylation. Pretreatment with 20 μM LY294002 (PI3K inhibitor) for 30 min inhibited phosphorylation of Akt, increased
migration by activating Rac1 in polyamine-depleted IEC-6 cells, and restored the actin structure similar to that in cells
grown in control medium. Treatment of cells with a GSK-3β inhibitor (AR-A014418) altered the actin cytoskeleton and inhibited
migration, mimicking the effects of polyamine depletion. Thus, our results indicate that sustained activation of Akt in response
to polyamine depletion inhibits migration through GSK-3β and Rac1.
Received 25 August 2006; received after revision 3 October 2006; accepted 16 October 2006 相似文献
15.
MurNAc etherases cleave the uniqued-lactyl ether bond of the bacterial cell wall sugar N-acetylmuramic acid (MurNAc). Members of this newly discovered family of enzymes are widely distributed among bacteria and
are required to utilize peptidoglycan fragments obtained either from the environment or from the endogenous cell wall (i.e.,
recycling). MurNAc etherases are strictly dependent on the substrate MurNAc possessing a free reducing end and a phosphoryl
group at C6. They carry a single conserved sugar phosphate isomerase/sugar phosphate- binding (SIS) domain to which MurNAc
6-phosphate is bound. Two subunits form an enzymatically active homodimer that structurally resembles the isomerase module
of the double-SIS domain protein GlmS, the glucosamine 6-phosphate synthase. Structural comparison provides insights into
the two-step lyase-type reaction mechanism of MurNAc etherases: β-elimination of the D-lactic acid substituent proceeds through
a 2,3-unsaturated sugar intermediate to which water is subsequently added.
Received 31 August 2007; received after revision 12 October 2007; accepted 1 November 2007 相似文献
16.
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
17.
Serglycin is a proteoglycan found in hematopoietic cells and endothelial cells. It has important functions related to formation
of several types of storage granules. In connective tissue mast cells the covalently attached glycosaminoglycan is heparin,
whereas mucosal mast cells and activated macrophages contain oversulfated chondroitin sulfate (type E). In mast cells, serglycin
interact with histamine, chymase, tryptase and carboxypeptidase, in neutrophils with elastase, in cytotoxic T cells with granzyme
B, in endothelial cells with tissue-type plasminogen activator and in macrophages with tumor necrosis factor-α. Serglycin
is important for the retention of key inflammatory mediators inside storage granules and secretory vesicles. Serglycin can
further modulate the activities of partner molecules in different ways after secretion from activated immune cells, through
protection, transport, activation and interactions with substrates or target cells. Serglycin is a proteoglycan with important
roles in inflammatory reactions.
Received 2 October 2007; received after revision 7 November 2007; accepted 12 November 2007 相似文献
18.
Sui Y Zhao HL Ma RC Ho CS Kong AP Lai FM Ng HK Rowlands DK Chan JC Tong PC 《Cellular and molecular life sciences : CMLS》2007,64(23):3119-3128
This study was performed to examine the effect of chronic renal impairment and renin-angiotensin system (RAS) activation induced
by unilateral nephrectomy (UNX) on the development of pancreatic islet β-cell deficit and glucose intolerance. Sprague-Dawley
rats were randomized into three groups: untreated UNX (n = 10), UNX treated with the angiotensin-converting enzyme inhibitor lisinopril (n = 8) and sham operation (n = 10). Blood glucose, serum insulin, renal function and histological changes of kidney and pancreas were examined 8 months
postoperation. Compared with the sham rats, UNX rats developed renal impairment, insulin deficiency and glucose intolerance.
Histological staining revealed an islet β-cell deficit associated with increased immunoreactivity for angiotensin and angiotensin
type 1 receptor in UNX rats. Treatment with lisinopril significantly improved renal dysfunction, hyperglycemia, insulin secretion
and islet RAS expression. These data suggest that chronic renal impairment and RAS activation may contribute to islet β-cell
loss and glucose intolerance. RAS blockade may therefore prevent these disorders.
Received 29 August 2007; received after revision 25 September 2007; accepted 27 September 2007 相似文献
19.
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
20.
The human hair follicle is composed of different concentric compartments, which reflect different programmes of differentiation.
Using monoclonal antibodies against α2β1 and α3β1 integrins we demonstrated a shift in their expression, from a basolateral distribution in the basal cells of the lower outer
root sheath, to an apicolateral expression in the upper outer root sheath, as in epidermis. This shift takes place in a transition
zone, localized to the midpart of the follicle. The distinct basolateral distribution of α2β1 and α3β1 integrins in the lower portion of the outer root sheath coincides with the presence of basal cell protrusions and is probably
linked to the presence of the vitreous membrane which surrounds the bottom part of the anagen human hair follicle. Moreover,
we showed that the expression of α6β4 integrin is discontinuous along the hair follicle and coincides with that of laminin 5. Together these results establish
that within a given compartment – namely the outer root sheath – several domains can be clearly identified, which probably
reflect the onset of successive differentiation pathways along the hair follicle.
Received 17 January 1997; received after revision 18 February 1997; accepted 24 February 1997 相似文献