共查询到20条相似文献,搜索用时 222 毫秒
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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
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Mohammed I Yeung A Abedin A Hopkinson A Dua HS 《Cellular and molecular life sciences : CMLS》2011,68(11):1941-1952
Antimicrobial peptides are host defence molecules that play a potential role in preventing infection at the epithelial surfaces.
Ribonuclease (RNase)-7 has been shown to possess a broad spectrum of microbicidal activity against various pathogens. Here,
we demonstrate that RNase-7 protein is localised to the superficial layers of ocular surface cells and increased in response
to interleukin (IL)-1β, suggesting an active role during inflammation related to ocular surface infection. Signal transduction
pathways involved in RNase-7 expression are unknown. Involvement of transforming growth factor β-activated kinase-1 (TAK-1)
activated nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) pathway molecules [c-Jun N-terminal kinase
(JNK), extracellular signal-regulated kinase (ERK) and p38] were studied because of their importance in infection and inflammation.
Blocking the MAPKs resulted in inhibition of RNase-7 expression in response to IL-1β. However, RNase-7 induction by IL-1β
was not affected by inhibiting the NF-κB signalling pathway. In conclusion, our results indicate that RNase-7 expression is
specifically mediated via MAPKs but not NF-κB signalling pathways. 相似文献
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Larrucea S Butta N Rodriguez RB Alonso-Martin S Arias-Salgado EG Ayuso MS Parrilla R 《Cellular and molecular life sciences : CMLS》2007,64(22):2965-2974
Podocalyxin (PODXL) is a mucin protein of the CD34 family expressed in kidney glomerular podocytes, vascular endothelium,
progenitor bone marrow and tumor cells. It is assumed that PODXL plays an anti-adherent role in kidney podocytes. CHO cells
stably expressing human PODXL (CHO-PODXL) or human tumor cells (Tera-1) inherently expressing PODXL showed increased adherence
to platelets. The adherence of cells was inhibited (70%) by blockers of platelet P-selectin, prevented by the soluble ectodomain
of human PODXL (PODXL-Δ) or by the arginine-glycine-aspartate (RGDS) peptide and partially impeded by inhibition of integrin
αVβ3/αVβ5, suggesting a coordinated action of P-selectin and integrins. Colocalization of platelet P-selectin and PODXL expressed
on CHO cells was demonstrated by confocal immunofluorescence. No adherence to platelets was observed when PODXL was expressed
in glycomutant CHO cells deficient in sialic acid.
Received 14 August 2007; received after revision 12 September 2007; accepted 13 September 2007 相似文献
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Strell C Lang K Niggemann B Zaenker KS Entschladen F 《Cellular and molecular life sciences : CMLS》2007,64(24):3306-3316
The extravasation of leukocytes and tumor cells is a multi-step process with the involvement of various adhesion molecules
depending on the three steps rolling, adhesion, and diapedesis. We have developed an in vitro model, by which we investigated the rolling and adhesion of neutrophil granulocytes and MDA-MB-468 human breast carcinoma
cells to lung endothelial cells under physiological flow-conditions. We found that norepinephrine had an inhibitory function
on the fMLP-promoted adhesion of neutrophil granulocytes due to a down-regulation of β2-integrin. Furthermore, neutrophil
granulocytes serve as linking cells for the interaction of the MDA-MB-468 cells with the endothelium, which are both β2-integrin
negative, but express the β2-integrin ligand ICAM-1. In addition, we show here that N-cadherin is up-regulated on the endothelial
cells and on neutrophil granulocytes in response to fMLP. This up-regulation resulted in a significant increase of adherent
MDA-MB-468 cells, which are also N-cadherin positive.
Received 3 September 2007; received after revision 17 October 2007; accepted 22 October 2007 相似文献
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The regulation of IL-17A and IL-22 production differs between human and murine γδ T cells. We find that human γδ T cells expressing
Vγ2Vδ2 T cell receptors are peripherally polarized to produce IL-17A or IL-22, much like CD4 αβ Th17 T cells. This requires
IL-6, IL-1β, and TGF-β, whereas expansion and maintenance requires IL-23, IL-1β, and TGF-β. In contrast, IL-17A and IL-22
production by murine γδ T cells is innately programmed during thymic ontogeny but requires IL-23 and IL-1β for maintenance.
Murine γδ cells producing IL-17A and IL-22 play important roles in microbial, autoimmune, and inflammatory responses. However,
the roles played by human IL-17A- and IL-22-producing γδ T cells are less clear but are also likely to be important. These
observations highlight differences between humans and murine γδ T cells and underscore the importance of IL-17A- and IL-22-producing
γδ T cells. 相似文献
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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
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Ramirez F Sakai LY Rifkin DB Dietz HC 《Cellular and molecular life sciences : CMLS》2007,64(18):2437-2446
Fibrillins are the structural components of extracellular microfibrils that impart physical properties to tissues, alone or
together with elastin as elastic fibers. Genetic studies in mice have revealed that fibrillin-rich microfibrils are also involved
in regulating developmental programs and homeostatic processes through the modulation of TGF-β/BMP signaling events. A new
paradigm has thus emerged whereby the spatiotemporal organization of microfibrils dictates both the cellular activities and
physical properties of connective tissues. These observations have paved the way to novel therapeutic approaches aimed at
counteracting the life-threatening complications in human conditions caused by dysfunctions of fibrillin-rich microfibrils.
Received 2 April 2007; received after revision 23 May 2007; accepted 24 May 2007 相似文献
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Ras proteins in the control of the cell cycle and cell differentiation 总被引:12,自引:0,他引:12
The Ras family of small GTPases includes three closely related proteins: H-, K-, and N-Ras. Ras proteins are involved in
the transduction of signals elicited by activated surface receptors, acting as key components by relaying signals downstream
through diverse pathways. Mutant, constitutively activated forms of Ras proteins are frequently found in cancer. While constitutive
Ras activation induces oncogenic-like transformation in immortalized fibroblasts, it causes growth arrest in primary vertebrate
cells. Induction of p53 and cyclin-dependent kinase inhibitors such as p15INK4b, p16INK4a, p19ARF, and p21WAF1 accounts for this response. Interestingly, while ras has usually been regarded as a transforming oncogene, the analysis of Ras function in most of the cellular systems studied
so far indicates that the promotion of differentiation is the most prominent effect of Ras. While in some cell types, particularly
muscle, Ras inhibits differentiation, in others such as neuronal, adipocytic, or myeloid cells, Ras induces differentiation,
in some cases accompanied by growth arrest. Several possible mechanisms for the pleiotropic effects of Ras in animal cells
are discussed.
Received 8 March 2000; received after revision 24 May 2000; accepted 24 May 2000 相似文献
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The role of ras and other low molecular weight guanine nucleotide (GTP)-binding proteins during hematopoietic cell differentiation 总被引:5,自引:0,他引:5
Recent progress in the understanding of signal transduction and gene regulation in hematopoietic cells has shown that many intracellular signalling pathways are modulated by low molecular weight guanine nucleotide (GTP)-binding proteins (LMWGs). LMWGs act as molecular switches for regulating a wide range of signal-transduction pathways in virtually all cells. In hematopoietic cells, LMWGs have been shown to participate in essential functions such as growth control, differentiation, cytoskeletal organization, cytokine and chemoattractant-induced signalling events, reduced nicotinamide adenine dinucleotide phosphate oxidase activity, intracellular vesicle transport and secretion. In human leukemias, myelodysplastic syndromes and myeloproliferative disorders, Ras activation occurs by point mutations, overexpression or by alteration of NF-1 Ras-GTPase activating protein (GAP). These are postinitiation events in leukemia but may modulate growth-factor-dependent and independent leukemic growth. Two animal models of mutated N-ras expression resulting in myelodysplastic and myeloproliferative features are discussed. The role of Ras in organ development is discussed in the context of transgenic knockout mice. More LMWG functions will certainly be identified as we gain a better understanding of regulatory pathways modulating myeloid signal transduction. This review will summarize our current understanding of this rapidly advancing area of research. 相似文献
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Integrins and cardiovascular disease 总被引:2,自引:0,他引:2
Cardiovascular diseases involve abnormal cell-cell interactions leading to the development of atherosclerotic plaque, which
when ruptured causes massive platelet activation and thrombus formation. Parts of a loose thrombus may detach to form an embolus,
blocking circulation at a more distant point. The integrins are a family of adhesive cell receptors interacting with adhesive
proteins or with counterreceptors on other cells. There is now solid evidence that the major integrin on platelets, the fibrinogen
receptor α
IIb
β
3 , has an important role in several aspects of cardiovascular diseases and that its regulated inhibition leads to a reduction
in incidence and mortality due to these disorders. The development of α
IIb
β
3 inhibitors is an important strategy of many pharmaceutical companies which foresee a large market for the treatment of acute
conditions in surgery, the symptoms of chronic conditions and, it is hoped, maybe even the successful prophylaxis of these
conditions. Although all the associated problems have not been solved, the undoubted improvements in patient care resulting
from the first of these treatments in the clinic have stimulated further research on the role of integrins on other vascular
cells in these processes and in the search for new inhibitors. Both the development of specific inhibitors and of mice with
specific integrin subunit genes ablated have contributed to a better understanding of the function of integrins in development
of the cardiovascular system. 相似文献
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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
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Signal regulation by family conspiracy 总被引:6,自引:0,他引:6
The signal regulating proteins (SIRPs) are a family of ubiquitously expressed transmembrane glycoproteins composed of two
subgroups: SIRPα and SIRPβ, containing more than ten members. SIRPα has been shown to inhibit signalling through a variety of receptors including receptor tyrosine kinases and cytokine receptors.
This function involves protein tyrosine kinases and is dependent on immunoreceptor tyrosine-based inhibition motifs which
recruit key protein tyrosine phosphatases to the membrane. Negative regulation by SIRPα may also involve its ligand, CD47, in a bi-directional signalling mechanism. The SIRPβ subtype has no cytoplasmic domain but instead associates with at least one other transmembrane protein (DAP-12, or KARAP).
DAP-12 possesses immunoreceptor tyrosine-based activation motifs within its cytoplasmic domain that are thought to link SIRPβ to activating machinery. SIRPα and SIRPβ thus have complementary roles in signal regulation and may conspire to tune the response to a stimulus.
Received 6 July 2000; revised 2 August 2000; accepted 5 August 2000 相似文献
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Ras GTPases mediate a wide variety of cellular processes by converting a multitude of extracellular stimuli into specific biological responses including proliferation, differentiation and survival. In mammalian cells, three ras genes encode four Ras isoforms (H-Ras, K-Ras4A, K-Ras4B and N-Ras) that are highly homologous but functionally distinct. Differences between the isoforms, including their post-translational modifications and intracellular sorting, mean that Ras has emerged as an important model system of compartmentalised signalling and membrane biology. Ras isoforms in different subcellular locations are proposed to recruit distinct upstream and downstream accessory proteins and activate multiple signalling pathways. Here, we summarise data relating to isoform-specific signalling, its role in disease and the mechanisms promoting compartmentalised signalling. Further understanding of this field will reveal the role of Ras signalling in development, cellular homeostasis and cancer and may suggest new therapeutic approaches. 相似文献
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Salminen A Ojala J Huuskonen J Kauppinen A Suuronen T Kaarniranta K 《Cellular and molecular life sciences : CMLS》2008,65(7-8):1049-1058
Research on aging in model organisms has revealed different molecular mechanisms involved in the regulation of the lifespan.
Studies on Saccharomyces cerevisiae have highlighted the role of the Sir2 family of genes, human Sirtuin homologs, as the longevity factors. In Caenorhabditis elegans, the daf-16 gene, a mammalian homolog of FoxO genes, was shown to function as a longevity gene. A wide array of studies has
provided evidence for a role of the activation of innate immunity during aging process in mammals. This process has been called
inflamm-aging. The master regulator of innate immunity is the NF-κB system. In this review, we focus on the several interactions
of aging-associated signaling cascades regulated either by Sirtuins and FoxOs or NF-κB signaling pathways. We provide evidence
that signaling via the longevity factors of FoxOs and SIRT1 can inhibit NF-κB signaling and simultaneously protect against inflamm-aging process.
Received 4 October 2007; received after revision 7 November 2007; accepted 9 November 2007 相似文献
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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
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Simms RJ Hynes AM Eley L Inglis D Chaudhry B Dawe HR Sayer JA 《Cellular and molecular life sciences : CMLS》2012,69(6):993-1009
Joubert syndrome and related diseases (JSRD) are cerebello-oculo-renal syndromes with phenotypes including cerebellar hypoplasia,
retinal dystrophy, and nephronophthisis (a cystic kidney disease). Mutations in AHI1 are the most common genetic cause of JSRD, with developmental hindbrain anomalies and retinal degeneration being prominent
features. We demonstrate that Ahi1, a WD40 domain-containing protein, is highly conserved throughout evolution and its expression
associates with ciliated organisms. In zebrafish ahi1 morphants, the phenotypic spectrum of JSRD is modeled, with embryos showing brain, eye, and ear abnormalities, together with
renal cysts and cloacal dilatation. Following ahi1 knockdown in zebrafish, we demonstrate loss of cilia at Kupffer’s vesicle and subsequently defects in cardiac left–right
asymmetry. Finally, using siRNA in renal epithelial cells we demonstrate a role for Ahi1 in both ciliogenesis and cell–cell
junction formation. These data support a role for Ahi1 in epithelial cell organization and ciliary formation and explain the
ciliopathy phenotype of AHI1 mutations in man. 相似文献
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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