共查询到20条相似文献,搜索用时 22 毫秒
1.
I. Campia E. Gazzano G. Pescarmona D. Ghigo A. Bosia C. Riganti 《Cellular and molecular life sciences : CMLS》2009,66(9):1580-1594
Digoxin and ouabain are steroid drugs that inhibit the Na+/K+-ATPase, and are widely used in the treatment of heart diseases. They may also have additional effects, such as on metabolism
of steroid hormones, although until now no evidence has been provided about the effects of these cardioactive glycosides on
the synthesis of cholesterol. Here we report that digoxin and ouabain increased the synthesis of cholesterol in human liver
HepG2 cells, enhancing the activity and the expression of the
3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR), the rate-limiting enzyme of the cholesterol synthesis. This effect
was mediated by the binding of the sterol regulatory element binding protein-2 (SREBP-2) to the HMGCR promoter, and was lost
in cells silenced for SREBP-2 or loaded with increasing amounts of cholesterol. Digoxin and ouabain competed with cholesterol
for binding to the SREBP-cleavage-activating protein, and are critical regulators of cholesterol synthesis in human liver
cells.
Received 10 January 2009; received after revision 11 February 2009; accepted 6 March 2009 相似文献
2.
M. Cintra-Francischinelli P. Pizzo L. Rodrigues-Simioni L. A. Ponce-Soto O. Rossetto B. Lomonte J. M. Gutiérrez T. Pozzan C. Montecucco 《Cellular and molecular life sciences : CMLS》2009,66(10):1718-1728
Snake myotoxins have a great impact on human health worldwide. Most of them adopt a phospholipase A2 fold and occur in two
forms which often co-exist in the same venom: the Asp49 toxins hydrolyse phospholipids, whilst Lys49 toxins are enzymatically
inactive. To gain insights into their mechanism of action, muscle cells were exposed to Bothrops myotoxins, and cytosolic Ca2+ and cytotoxicity were measured. In both myoblasts and myotubes, the myotoxins induced a rapid and transient rise in cytosolic
[Ca2+], derived from intracellular stores, followed, only in myotubes, by a large Ca2+ influx and extensive cell death. Myoblast viability was unaffected. Notably, in myotubes Asp49 and Lys49 myotoxins acted
synergistically to increase the plasma membrane Ca2+ permeability, inducing cell death. Therefore, these myotoxins may bind to acceptor(s) coupled to intracellular Ca2+ mobilization in both myoblasts and myotubes. However, in myotubes only, the toxins alter plasma membrane permeability, leading
to death.
Received 21 January 2009; received after revision 05 March 2009; accepted 11 March 2009 相似文献
3.
G. Zhao X.-W. Zheng G.-W. Qin Y. Gai Z.-H. Jiang L.-H. Guo 《Cellular and molecular life sciences : CMLS》2009,66(9):1617-1629
Cocktail recipes containing Psoralea corylifolia seeds (PCS) are used to empirically treat Parkinson disease. A PCS isolate Δ3,2-hydroxybakuchiol (BU) can inhibit dopamine uptake in dopamine transporter (DAT) transfected Chinese hamster ovary (CHO)
cells, and dopamine reuptake blockade may provide an alternative approach for ameliorating parkinsonism. Here, we assessed
the potential dopaminergic neuroprotective, and antiparkinsonian-like activity of BU. BU sample size was increased by using
a scale-up extraction paradigm. Pharmacologically, BU significantly protected SK-N-SH cells from 1-methyl-4-phenylpyridinium
(MPP+) insult, produced striking inhibitory actions on dopamine/norepinephrine uptake and WIN35,428 binding in synaptosomes on
in vivo administration, and significantly preventing poor performance on rotarod and dopaminergic loss in substantia nigra in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
(MPTP) mice. BU acts by protecting dopaminergic neurons from MPP+ injury and preventing against MPTP-induced behavioral and histological lesions in the Parkinson’s disease (PD) model, possibly
by inhibiting monoamine transporters. These findings suggest that BU could be meaningful in PD treatment.
Received 14 January 2009; received after revision 22 February 2009; accepted 10 March 2009 相似文献
4.
E. Sick N. Niederhoffer K. Takeda Y. Landry J.-P. Gies 《Cellular and molecular life sciences : CMLS》2009,66(7):1271-1282
Mast cells play pivotal roles in allergic and inflammatory processes via distinct activation pathways. Mucosal and serosal mast cells are activated by the IgE/FcɛRI pathway, while only serosal mast
cells are activated by basic secretagogues. We show that CD47 receptors are expressed on rat peritoneal mast cells. 4N1K,
a peptide agonist of CD47, rapidly caused exocytosis. Such exocytosis required increased intracellular calcium and was inhibited
by pertussis toxin and an antibody against the βγ dimer of a Gi protein. Cooperation with integrins and glycosylphosphatidylinositol-anchored proteins was necessary, since anti-integrin
antibodies and pretreatment with phosphatidylinositol-phospholipase C reduced exocytosis. Depletion of membrane cholesterol
inhibited exocytosis and decreased CD47 in lipid rafts, consistent with a CD47/integrin/Gi protein complex being located in rafts. An anti-CD47 antibody inhibited exocytosis induced by 4N1K and by mastoparan and
spermine, suggesting that basic secretagogues might target CD47. We propose that 4N1K-stimulated mast cell exocytosis involves
a CD47/integrin/Gi protein complex.
Received 8 December 2008; received after revision 12 January 2009; accepted 29 January 2009 相似文献
5.
Sp?tzle, a dimeric ligand, binds to the Drosophila Toll receptor and activates the signal pathway functioning in both embryonic patterning and innate immunity. Here, we used
the evolutionary trace approach based on phylogenetic information to predict the evolutionary epitope of Sp?tzle and found
that it mainly clusters in several adjacent loops of Sp?tzle far from the cystine-knot structural domain. We designed six
mutants of Sp?tzle based on the evolutionary epitope and transfected them into a stable cell line expressing the luciferase
reporter gene under the control of the drosomycin promoter. Luciferase assays showed that these mutants cannot significantly activate the drosomycin promoter, suggesting the involvement of these sites in binding of Sp?tzle to the Toll receptor. These data highlight the
importance of the Trp-loop of the mushroom-shaped Sp?tzle dimer in Toll receptor activation and demonstrate that evolution-guided
site-specific mutagenesis represents a useful and promising strategy for understanding the ligand-receptor interaction.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.
Received 14 January 2009; received after revision 14 February 2009; accepted 09 March 2009 相似文献
6.
Matin A 《Cellular and molecular life sciences : CMLS》2007,64(11):1317-1322
The 129 mouse strain develops congenital testicular germ cell tumors (TGCTs) at a low frequency. TGCTs in mice resemble the
testicular tumors (teratomas) that occur in human infants. The genes that cause these tumors in 129 have not been identified.
The defect at the Ter locus increases TGCT incidence such that 94% of 129-Ter/Ter males develop TGCTs. The primary effect of the Ter mutation is progressive loss of primordial germ cells (PGCs) during embryonic development. This results in sterility in adult
Ter/Ter mice on all mouse strain backgrounds. However, on the 129 background, Ter causes tumor development in addition to sterility. Therefore, Ter acts as a modifier of 129-derived TGCT susceptibility genes. Ter was identified to be a mutation that inactivates the Dead-end1 (Dnd1) gene. In this perspective, I discuss the possible areas of future investigations to elucidate the mechanism of TGCT development
due to Dnd1 inactivation.
Received 29 September 2006; received after revision 29 January 2007; accepted 19 February 2007 相似文献
7.
Multiple roles of the DSCR1 (Adapt78 or RCAN1) gene and its protein product Calcipressin 1 (or RCAN1) in disease 总被引:5,自引:0,他引:5
The DSCR1 (Adapt78) gene1 is transiently induced by stresses to temporarily protect cells against further potentially lethal challenges. However, chronic
expression of the DSCR1 (Adapt78) gene has now been implicated in several pathological conditions including Alzheimer’s disease, Down syndrome and cardiac
hypertrophy. Calcipressin 1 has been shown to function through direct binding and inhibition of the serine threonine protein
phosphatase Calcineurin. Pharmacological inhibition of calcineurin, by the immunosuppressive drugs cyclosporin A and FK506,
affects a wide variety of diseases. It is, therefore, likely that this endogenous calcineurin inhibitor, calcipressin 1, may
also play a role in a variety of human diseases.
1Please note that the mammalian DSCR1 gene is also called Adapt78 or RCAN1, and its protein products have been named Calcipressin1, MCIP1 and RCAN1. A proposal to adopt a single gene name of RCAN1 and a protein name RCAN1 (for Regulator of Calcineurin) has been endorsed by the HUGO Gene Nomenclature Committee, but final
approval must await agreement from a majority of researchers in the field.
Received 2 March 2005; received after revision 27 May 2005; accepted 19 July 2005 相似文献
8.
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
9.
Human bystin was identified as a cytoplasmic protein directly binding to trophinin, a cell adhesion molecule potentially involved
in human embryo implantation. Although the trophinin gene is unique to mammals, the bystin gene (BYSL) is conserved across eukaryotes. Recent studies show that bystin plays a key role during the transition from silent trophectoderm
to an active trophoblast upon trophinin-mediated cell adhesion. Bystin gene knockout and knockdown experiments demonstrate
that bystin is essential for embryonic stem cell survival and trophectoderm development in the mouse. Furthermore, biochemical
analysis of bystin in human cancer cells and mouse embryos indicates a function in ribosomal biogenesis, specifically in processing
of 18S RNA in the 40S subunit. Strong evidence that BYSL is a target of c-MYC is consistent with a role for bystin in rapid protein synthesis, which is required for actively growing
cells.
Received 30 June 2007; received after revision 7 August 2007; accepted 29 August 2007 相似文献
10.
Page NM 《Cellular and molecular life sciences : CMLS》2004,61(13):1652-1663
The mammalian tachykinins are a family of peptides that, until recently, has included substance P (SP), neurokinin A and neurokinin B. Since, the discovery of a third preprotachykinin gene (TAC4), the number of tachykinins has more than doubled to reveal several species-divergent peptides. This group includes hemokinin-1 (HK-1) in mouse and rat, endokinin-1 (EK-1) in rabbit, and EKA, EKB, human HK-1 (hHK-1) and hHK(4–11) in humans. Each exhibits a remarkable selectivity and potency for the tachykinin NK1 receptor similar to SP. Their peripheral expression has led to the proposal that they are the endogenous peripheral SP-like endocrine/paracrine agonists where SP is not expressed. Moreover, their strong cross-reactivity with a specific SP antibody leads us to question many of the proposed locations and roles of SP in the periphery. Additionally, three orphan tachykinin gene-related peptides are identified on TAC4, in rabbit, EK-2 and in humans, EKC and EKD.Received 25 January 2004; received after revision 18 February 2004; accepted 27 February 2004 相似文献
11.
Dolezel D Zdechovanova L Sauman I Hodkova M 《Cellular and molecular life sciences : CMLS》2008,65(6):964-969
Current models state that insect peripheral oscillators are directly responsive to light, while mammalian peripheral clock
genes are coordinated by a master clock in the brain via intermediate factors, possibly hormonal. We show that the expression
levels of two circadian clock genes, period (per) and Par Domain Protein 1 (Pdp1) in the peripheral tissue of an insect model species, the linden bug Pyrrhocoris apterus, are inversely affected by contrasting photoperiods. The effect of photoperiod on per and Pdp1 mRNA levels was found to be mediated by the corpus allatum, an endocrine gland producing juvenile hormone. Our results
provide the first experimental evidence for the effect of an endocrine gland on circadian clock gene expression in insects.
Received 31 October 2007; received after revision 7 January 2008; accepted 9 January 2008
D. Dolezel, L. Zdechovanova: These authors contributed equally to this work. 相似文献
12.
S. P. Yun M. Y. Lee J. M. Ryu H. J. Han 《Cellular and molecular life sciences : CMLS》2009,66(9):1603-1616
Identifying the small molecules that permit precise regulation of embryonic stem (ES) cell proliferation should further support
our understanding of the underlying molecular mechanisms of self renewal. In the present study, we showed that PGE2 increased [3H]-thymidine incorporation in a time and dose dependent manner. In addition, PGE2 increased the expression of cell cycle regulatory proteins, the percentage of cells in S phase and the total number of cells.
PGE2 obviously increased E-type prostaglandin (EP) receptor 1 mRNA expression level compare to 2, 3, 4 subtypes. EP1 antagonist
also blocked PGE2-induced cell cycle regulatory protein expression and thymidine incorporation. PGE2 caused phosphorylation of protine kinase C, Src, epidermal growth factor (EGF) receptor, phosphatidylinositol 3-kinase (PI3K)/Akt
phosphorylation, and p44/42 mitogen-activated protein kinase (MAPK), which were blocked by each inhibitors. In conclusion,
PGE2-stimulated proliferation is mediated by MAPK via EP1 receptor-dependent PKC and EGF receptor-dependent PI3K/Akt signaling
pathways in mouse ES cells.
Received 30 January 2009; received after revision 03 March 2009; accepted 10 March 2009 相似文献
13.
Hu QD Lu H Huo K Ying K Li J Xie Y Mao Y Li YY 《Cellular and molecular life sciences : CMLS》2003,60(8):1725-1732
The Saccharomyces cerevisiae TPT1 gene plays a role in removing the 2-phosphate from ligated tRNA during the maturation of pre-tRNA. Here we reported the cloning and characterization of the human TRPT1 gene as a homolog of yeast TPT1. The TRPT1 gene is located at human chromosome 11q13 and encodes a polypeptide of 253 amino acids. BLAST searches with its amino acid sequence revealed the ubiquitous occurrence of TRPT1 homologs and their functional relationships with the presence of the DUF60/KptA domain. Northern analysis demonstrated that the gene is primarily expressed in heart and skeletal muscle, with lower or undetectable levels in other tissues studied. A plasmid-shuffling experiment showed that the human TRPT1 gene could complement the tpt1 mutation in S. cerevisiaeReceived 19 March 2003; received after revision 25 April 2003; accepted 22 May 2003 相似文献
14.
Malaguarnera L 《Cellular and molecular life sciences : CMLS》2006,63(24):3018-3029
The enzyme chitotriosidase (ChT), the human analogue of chitinases from non-vertebrate species, is one of the most abundant
and indicative proteins secreted by activated macrophages. Its enzymatic activity is elevated in serum of patients suffering
from Gaucher’s disease type 1 and in some other inherited lysosomal storage disorders, as well as in diseases in which macrophages
are activated. The last decade has witnessed the appearance of a substantial number of studies attempting to unravel its cellular
functions, which have yet not been fully defined. A great deal of progress has been made in the study of the physiological
roles of ChT. This review is looks at the key areas of investigations addressed to further illuminate whether ChT activation
might have different functional meanings in various diseases.
Received 7 June 2006; received after revision 24 July 2006; accepted 21 September 2006 相似文献
15.
Molecular characterization and expression of the antimicrobial peptide defensin from the housefly (Musca domestica) 总被引:2,自引:0,他引:2
Wang JX Zhao XF Liang YL Li L Zhang W Ren Q Wang LC Wang LY 《Cellular and molecular life sciences : CMLS》2006,63(24):3072-3082
A 430-bp cDNA encoding the insect antimicrobial peptide defensin was cloned from the housefly, and designated Musca domestica defensin (Mdde). The open reading frame of the cDNA encoded a 92-amino acid peptide with an N-terminal signal sequence followed by a propeptide
that is processed by cleavage to a 40-amino acid mature peptide. Northern analysis and in situ hybridization identified the corresponding mRNA in the fat body of bacterially challenged houseflies and in the epidermis
of the body wall of naive and challenged houseflies. The Gram-negative bacterium (Escherichia coli) is a strong inducer of the gene. By RT-PCR, Mdde mRNA was also detected in naive and challenged insects. These findings suggest that the defensin gene is constitutively expressed
in the epidermis of the housefly body wall. The predicted mature form of Mdde was expressed as a recombinant peptide in E. coli and Pichia pastoris. The recombinant Mdde expressed in Pichia was active against Gram-positive and some Gram-negative bacteria.
Received 20 June 2006; received after revision 3 October 2006; accepted 30 October 2006 相似文献
16.
The surfaces of mammalian cells are covered by a variety of carbohydrates linked to proteins
and lipids. N-glycans are commonly found carbohydrates in plasma
membrane proteins. The structure and biosynthetic pathway of
N-glycans have been analyzed extensively. However, functional
analysis of cell surface N-glycans is just under way with recent
studies of targeted disruption of genes involved in N-glycan
synthesis. This review briefly introduces the potential role of processing -mannosidases
in N-glycan biosynthesis and recent findings derived from the
-mannosidase IIx (MX) gene knockout mouse, which shows male infertility. Thus, the MX gene
knockout experiment unveiled a novel function of specific
N-glycan, which is
N-acetylglucosamine-terminated and fucosylated triantennary
structure, in the adhesion between germ cells and Sertoli cells. Analysis of the MX gene knockout
mouse is a good example of a multidisciplinary approach leading to a novel discovery in the
emerging field of glycobiology.Received 29 November 2002; received after revision 30 December 2002; accepted 20 January 2003 相似文献
17.
18.
Genetic analysis of the nematode Caenorhabditis elegans reveals that all dpy-5 alleles are dominant suppressors of bli-4 blistering. Molecular cloning of dpy-5 establishes that it encodes a cuticle procollagen, defects in which are responsible for the short-body, dumpy phenotype.
The null mutation, e907 removes the entire coding region, whereas the dpy-5 reference allele, e61, contains a nonsense substitution. RT-PCR analysis and a dpy-5::gfp fusion show that dpy-5 is expressed only in hypodermal cells at all post-embryonic life-cycle stages. Variable expression of dpy-5 in V lineage-derived seam cells suggests an alternative regulatory mechanism in these cells. The dpy-5 gene product contains an Arg-X-X-Arg cleavage motif that could be recognized by a proprotein convertase, such as BLI-4. Mutation
of this site cause a dominant dumpy phenotype suggesting Dpy-5 procollagen requires processing for normal cuticle production.
Received 13 January 2006; accepted 23 March 2006 相似文献
19.
W. E. G. Müller M. Kasueske X. Wang H. C. Schröder Y. Wang D. Pisignano M. Wiens 《Cellular and molecular life sciences : CMLS》2009,66(3):537-552
Two classes of sponges (animal phylum Porifera) possess a siliceous skeleton which is composed of spicules. Studying the optical
fiber-mechanical properties of large spicules from hexactinellid sponges (> 5 cm) it was demonstrated that they are effective
light-collecting optical fibers. Here, we report that the demosponge Suberites domuncula is provided with a biosensor system composed of the (organic) light producing luciferase and the (inorganic) light transducing
silica spicules. The light transmission feature of these smaller spicules (200 μm) has been demonstrated and the ability of
sponge tissue to generate light has been proven. Screening for a luciferase gene in S. domuncula was successful; the recombinant luciferase was prepared and shown to be bioactive. The luciferase protein is abundantly present
in the close neighborhood of the spicules. The expression of the luciferase gene is under the control of light.
Received 14 August 2008; received after revision 09 November 2008; accepted 26 November 2008 相似文献