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Molecular Link (molecular + link)
Selected AbstractsMolecular link of different stages of the trematode host of Neorickettsia risticii to Acanthatrium oregonenseENVIRONMENTAL MICROBIOLOGY, Issue 8 2008Kathryn E. Gibson Summary Neorickettsia risticii, the obligatory intracellular bacterium that causes Potomac horse fever, has been detected in various developmental stages of digenetic trematodes in the environment. Neorickettsia risticii -infected gravid trematodes were identified as Acanthatrium oregonense, based on morphologic keys. However, whether immature trematodes harbouring N. risticii are also A. oregonense was unknown. The objective of this study was to infer the life cycle of N. risticii -positive trematode hosts and transstadial transmission of the bacterium by molecularly characterizing the relationship among adult and immature stages of trematodes confirmed infected with N. risticii. Sequences of 18S ribosomal RNA genes up to 1922 bp in size were obtained from infected adult gravid trematodes, sporocysts and cercariae, and metacercariae. The sequences from the different immature stages of trematode are closely related to those of adult trematodes, some with 100% sequence identity; thus, they likely are life stages of A. oregonense. Comparisons with known 18S ribosomal RNA gene sequences of other digenetic trematodes indicated that all tested stages of the N. risticii -positive trematodes belong to the family Lecithodendriidae, supporting the morphological identification. [source] Molecular links between tumor angiogenesis and inflammation: inflammatory stimuli of macrophages and cancer cells as targets for therapeutic strategyCANCER SCIENCE, Issue 8 2008Mayumi Ono Both inflammation and angiogenesis are exacerbated by increased production of chemokines/cytokines, growth factors, proteolytic enzymes, proteoglycans, lipid mediators and prostaglandins. It has been reported that approximately 15,20% of all malignancies are initiated or exacerbated by inflammation. Initiation and progression of cancer are also closely linked to angiogenesis. Infiltration of macrophages is a dramatic and common feature of inflammation, angiogenesis and cancer, and has been recently highlighted in an attempt to develop novel strategies for treating cancer. The recruitment and infiltration of macrophages in the tumor microenvironment activates them to support the malignant progression of cancer cells, and these macrophages are called tumor-associated macrophages. In a model of experimental angiogenesis using mouse corneas, macrophages infiltrated tissue in response to inflammatory cytokines and produced chemokines and angiogenesis-promoting factors, such as vascular endothelial growth factor-A, interleukin-8, matrix metalloproteinases, prostanoids and reactive oxygen species. Moreover, in a cancer xenograft model, inflammatory stimuli by a representative inflammatory cytokine, interleukin-1,, enhanced tumor growth and angiogenesis with infiltration and activation of macrophages. Co-culture of cancer cells with macrophages synergistically stimulated production of various angiogenesis-related factors when stimulated by the inflammatory cytokine. This inflammatory angiogenesis in both mouse cornea and a tumor model was mediated, in part, by activation of nuclear factor ,B and activator protein 1 (Jun/Fos). Administration of either nuclear factor ,B-targeting drugs or cyclooxygenase 2 inhibitors or depletion of macrophages could block both inflammatory angiogenesis and tumor angiogenesis. Thus, both inflammatory and angiogenic responses in tumor stroma could be targets for development of anticancer therapeutic drugs. (Cancer Sci 2008; 99: 1501,1506) [source] Transcriptional control of the pvdS iron starvation sigma factor gene by the master regulator of sulfur metabolism CysB in Pseudomonas aeruginosaENVIRONMENTAL MICROBIOLOGY, Issue 6 2010Francesco Imperi Summary In the Gram-negative pathogen Pseudomonas aeruginosa, the alternative sigma factor PvdS acts as a key regulator of the response to iron starvation. PvdS also controls P. aeruginosa virulence, as it drives the expression of a large set of genes primarily implicated in biogenesis and transport of the pyoverdine siderophore and synthesis of extracellular factors, such as protease PrpL and exotoxin A. Besides the ferric uptake regulatory protein Fur, which shuts off pvdS transcription under iron-replete conditions, no additional regulatory factor(s) controlling the pvdS promoter activity have been characterized so far. Here, we used the promoter region of pvdS as bait to tentatively capture, by DNA-protein affinity purification, P. aeruginosa proteins that are able to bind specifically to the pvdS promoter. This led to the identification and functional characterization of the LysR-like transcription factor CysB as a novel regulator of pvdS transcription. The CysB protein directly binds to the pvdS promoter in vitro and acts as a positive regulator of PvdS expression in vivo. The absence of a functional CysB protein results in about 50% reduction of expression of PvdS-dependent virulence phenotypes. Given the role of CysB as master regulator of sulfur metabolism, our findings establish a novel molecular link between the iron and sulfur regulons in P. aeruginosa. [source] BimEL as a possible molecular link between proteasome dysfunction and cell death induced by mutant huntingtinEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 11 2010Rebecca Leon Abstract Huntington's disease (HD) is a devastating neurodegenerative disorder caused by an expanded polyglutamine repeat within the N-terminus of the huntingtin protein. It is characterized by a selective loss of medium spiny neurons in the striatum. It has been suggested that impaired proteasome function and endoplasmic reticulum (ER) stress play important roles in mutant huntingtin (mHtt)-induced cell death. However, the molecular link involved is poorly understood. In the present study, we identified the essential role of the extra long form of Bim (Bcl-2 interacting mediator of cell death), BimEL, in mHtt-induced cell death. BimEL protein expression level was significantly increased in cell lines expressing the N-terminus of mHtt and in a mouse model of HD. Although quantitative RT-PCR analysis indicated that BimEL mRNA was increased in cells expressing mHtt, we provided evidence showing that, at the post-translational level, phosphorylation of BimEL played a more important role in regulating BimEL expression. Up-regulation of BimEL facilitated the translocation of Bax to the mitochondrial membrane, which further led to cytochrome c release and cell death. On the other hand, knocking down BimEL expression prevented mHtt-induced cell death. Taken together, these findings suggest that BimEL is a key element in regulating mHtt-induced cell death. A model depicting the role of BimEL in linking mHtt-induced ER stress and proteasome dysfunction to cell death is proposed. [source] Interaction between Lim15/Dmc1 and the homologue of the large subunit of CAF-1 , a molecular link between recombination and chromatin assembly during meiosisFEBS JOURNAL, Issue 9 2008Satomi Ishii In eukaryotes, meiosis leads to genetically variable gametes through recombination between homologous chromosomes of maternal and paternal origin. Chromatin organization following meiotic recombination is critical to ensure the correct segregation of homologous chromosomes into gametes. However, the mechanism of chromatin organization after meiotic recombination is unknown. In this study we report that the meiosis-specific recombinase Lim15/Dmc1 interacts with the homologue of the largest subunit of chromatin assembly factor 1 (CAF-1) in the basidiomycete Coprinopsis cinerea (Coprinus cinereus). Using C. cinerea LIM15/DMC1 (CcLIM15) as the bait in a yeast two-hybrid screen, we have isolated the C. cinerea homologue of Cac1, the largest subunit of CAF-1 in Saccharomyces cerevisiae, and named it C. cinerea Cac1-like (CcCac1L). Two-hybrid assays confirmed that CcCac1L binds CcLim15 in vivo. ,-Galactosidase assays revealed that the N-terminus of CcCac1L preferentially interacts with CcLim15. Co-immunoprecipitation experiments showed that these proteins also interact in the crude extract of meiotic cells. Furthermore, we demonstrate that, during meiosis, CcCac1L interacts with proliferating cell nuclear antigen (PCNA), a component of the DNA synthesis machinery recently reported as an interacting partner of Lim15/Dmc1. Taken together, these results suggest a novel role of the CAF-1,PCNA complex in meiotic events. We propose that the CAF-1,PCNA complex modulates chromatin assembly following meiotic recombination. [source] Dual action of apolipoprotein E-interacting HCCR-1 oncoprotein and its implication for breast cancer and obesityJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 9b 2009Seon-Ah Ha Abstract Obese women have an increased risk for post-menopausal breast cancer. The physiological mechanism by which obesity contributes to breast tumourigenesis is not understood. We previously showed that HCCR-1 oncogene contributes to breast tumourigenesis as a negative regulator of p53 and detection of HCCR-1 serological level was useful for the diagnosis of breast cancer. In this study, we found that the HCCR-1 level is elevated in breast cancer tissues and cell lines compared to normal breast tissues. We identified apolipoprotein E (ApoE) interacting with HCCR-1. Our data show that HCCR-1 inhibits anti-proliferative effect of ApoE, which was mediated by diminishing ApoE secretion of breast cancer cells. Finally, HCCR-1 induced the severe obesity in transgenic mice. Those obese mice showed severe hyperlipidaemia. In conclusion, our results suggest that HCCR-1 might play a role in the breast tumourigenesis while the overexpression of HCCR-1 induces the obesity probably by inhibiting the cholesterol-lowering effect of ApoE. Therefore, HCCR-1 seems to provide the molecular link between the obesity and the breast cancer risk. [source] Osterix is a key target for mechanical signals in human thoracic ligament flavum cellsJOURNAL OF CELLULAR PHYSIOLOGY, Issue 3 2007Dongwei Fan Mechanical stress is considered to be an important factor in the progression of thoracic ossification of the ligament flavum (TOLF). To elucidate the mechanism underlying mechanical stress-induced TOLF, we investigated the effect of stretching on cultured flavum ligament cells derived from TOLF and non-TOLF patients. We found that the mRNA expression of alkaline phosphatase (ALP), osteocalcin, Runx2, and osterix, but not that of Dlx5 and Msx2, was significantly increased by stretching in TOLF cells. In addition, the effect seems to be finely tuned by stretching-triggered activation of distinct mitogen-activated protein kinase cascades. Specifically, a p38 specific inhibitor, SB203580, significantly inhibited stretching-induced osterix expression as well as ALP activity, whereas a specific inhibitor of ERK1/2, U0126, prevented stretching-induced Runx2 expression. We showed that overexpression of osterix resulted in a significant increase of ALP activity in TOLF cells, and osterix-specific RNAi completely abrogated the stretching-induced ALP activity, indicating that osterix plays a key role in stretching-stimulated osteogenic effect in TOLF cells. These results suggest that mechanical stress plays important roles in the progression of TOLF through induction of osteogenic differentiation of TOLF cells, and our findings support that osterix functions as a molecular link between mechanostressing and osteogenic differentiation. J. Cell. Physiol. 211: 577,584, 2007. © 2007 Wiley-Liss, Inc. [source] The mammalian acrosome as a secretory lysosome: New and old evidenceMOLECULAR REPRODUCTION & DEVELOPMENT, Issue 11 2006Ricardo D Moreno Abstract The morphological and biochemical characteristics of the acrosome depart well from any other vesicles in somatic cells, making it one of a kind amongst secretory vesicles. The components of the acrosome include a mixture of unique enzymes like acrosin and other enzymes that when present in somatic cells are commonly found in lysosomes, peroxisomes, and even in the cytoplasm. Several observations have pointed out that acrosomal biogenesis has unique features not previously described in secretory vesicle biogenesis of somatic cells. In this review we discuss the evidence supporting a molecular link between the machinery involved in lysosome and acrosome biogenesis, link which may help account for the acrosome unique composition. Mol. Reprod. Dev. 73: 1430,1434, 2006. © 2006 Wiley-Liss, Inc. [source] Association by guilt: identification of DLX5 as a target for MeCP2 provides a molecular link between genomic imprinting and Rett syndromeBIOESSAYS, Issue 7 2005Sharmila Bapat Rett syndrome (RTT) is an X-linked dominant neurodevelopmental disorder affecting almost exclusively girls. Although mutations in methyl-CpG-binding protein (MeCP2) are known to be associated with RTT, gene expression patterns are not significantly altered in MeCP2-deficient cells. A recent study1 identified MeCP2-mediated histone modification and formation of a higher-order chromatin loop structure specifically associated with silent chromatin at the Dlx5,Dlx6 locus in normal cells, and its absence thereof in RTT patients. This altered expression of Dlx5 through loss of silent chromatin loop formation provides a molecular mechanism underlying RTT and proposes a novel role for MeCP2 in chromatin organization and imprinting. © 2005 Wiley Periodicals, Inc. BioEssays 27:676,680, 2005. © 2005 Wiley Periodicals, Inc. [source] Shugoshin: a centromeric guardian senses tensionBIOESSAYS, Issue 6 2005Sarah E. Goulding To ensure accurate chromosome segregation during mitosis, the spindle checkpoint monitors chromosome alignment on the mitotic spindle. Indjeian and colleagues have investigated the precise role of the shugoshin 1 protein (Sgo1p) in this process in budding yeast.1 The Sgo proteins were originally identified as highly conserved proteins that protect cohesion at centromeres during the first meiotic division. Together with other recent findings,2 the study highlighted here has identified Sgo1 as a component that informs the mitotic spindle checkpoint when spindle tension is perturbed. This discovery has provided a molecular link between sister chromatid cohesion and tension-sensing at the kinetochore,microtubule interface. BioEssays 27:588,591, 2005. © 2005 Wiley Periodicals, Inc. [source] Oxidative stress as a multiple effector in Fanconi anaemia clinical phenotypeEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 2 2005Giovanni Pagano Abstract:, Fanconi anaemia (FA) is a genetic disease characterised by bone marrow failure with excess risk of myelogenous leukaemia and solid tumours. A widely accepted notion in FA research invokes a deficiency of response to DNA damage as the fundamental basis of the ,crosslinker sensitivity' observed in this disorder. However, such an isolated defect cannot readily account for the full cellular and clinical phenotype, which includes a number of other abnormalities, such as malformations, endocrinopathies, and typical skin spots. An extensive body of evidence pointing toward an involvement of oxidative stress in the FA phenotype includes the following: (i) In vitro and ex vivo abnormalities in a number of redox status endpoints; (ii) the functions of several FA proteins in protecting cells from oxidative stress; (iii) redox-related toxicity mechanisms of the xenobiotics evoking excess toxicity in FA cells. The clinical features in FA and the in vivo abnormalities of redox parameters are here reconsidered in view of the pleiotropic clinical phenotype and known biochemical and molecular links to an in vivo prooxidant state, which causes oxidative damage to biomolecules, resulting in an excessive number of acquired abnormalities that may overwhelm the cellular repair capacity rather than a primary deficiency in DNA repair. FA may thus represent a unique model disease in testing the integration between the acquisition of macromolecular damage as a result of oxidative stress and the ability of the mammalian cell to respond effectively to such damage. [source] | |||||||||||||