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1.
Yuan J Dong Z Guo JP McGeehan J Xiao X Wang J Cali I McGeer PL Cashman NR Bessen R Surewicz WK Kneale G Petersen RB Gambetti P Zou WQ 《Cellular and molecular life sciences : CMLS》2008,65(4):631-643
Human prion diseases are characterized by the accumulation in the brain of proteinase K (PK)-resistant prion protein designated
PrP27 – 30 detectable by the 3F4 antibody against human PrP109 – 112. We recently identified a new PK-resistant PrP species,
designated PrP*20, in uninfected human and animal brains. It was preferentially detected with the 1E4 antibody against human PrP 97 – 108 but
not with the anti-PrP 3F4 antibody, although the 3F4 epitope is adjacent to the 1E4 epitope in the PrP*20 molecule. The present study reveals that removal of the N-terminal amino acids up to residue 91 significantly increases accessibility
of the 1E4 antibody to PrP of brains and cultured cells. In contrast to cells expressing wild-type PrP, cells expressing pathogenic
mutant PrP accumulate not only PrP*20 but also a small amount of 3F4-detected PK-resistant PrP27 – 30. Remarkably, during the course of human prion disease, a
transition from an increase in 1E4-detected PrP*20 to the occurrence of the 3F4-detected PrP27 – 30 was observed. Our study suggests that an increase in the level of PrP*20 characterizes the early stages of prion diseases.
Received 17 October 2007; received after revision 5 December 2007; accepted 14 December 2007 相似文献
2.
F. E. Weber J. H. Dyer F. López García M. Werder T. Szyperski K. Wüthrich H. Hauser 《Cellular and molecular life sciences : CMLS》1998,54(7):751-759
The preform of the rabbit sterol carrier protein 2 (pre-rSCP2) was cloned, the uniformly 15N-labelled protein expressed in Escherichia coli and studied by three-dimensional 15N-resolved nuclear magnetic resonance spectroscopy. In spite of its low solubility in aqueous solution of only ∼0.3 mM, sequential
15N and 1H backbone resonance assignments were obtained for 105 out of the 143 residues. From comparison of the sequential and medium-range
nuclear Overhauser effects (NOEs) in the two proteins, all regular secondary structures previously determined in mature human
SCP2 (hSCP2) [Szyperski et al. (1993) FEBS Lett. 335: 18–26] were also identified in pre-rSCP2. Near-identity of the backbone 15N and 1H chemical shifts and 1 : 1 correspondence of 24 long-range NOEs to backbone amide groups in the two proteins show that the
residues 21 – 143 adopt the same globular fold in pre-rSCP2 and mature hSCP2. The N-terminal 20-residue leader peptide of pre-rSCP2 is flexibly disordered in solution and does not observably affect the conformation of the polypeptide segment 21 – 143.
Received 11 May 1998; accepted 15 May 1998 相似文献
3.
The public perception of selenium has changed significantly over the last decades. Originally mainly known for its high toxicity,
it was later recognized as an essential trace element and is now (despite its narrow therapeutic window) almost being marketed
as a lifestyle drug. Indeed, some clinical and preclinical studies suggest that selenium supplementation may be beneficial
in a large number of clinical conditions. However, its mode of action is unresolved in most of these cases. Selenocysteine
– identified as the 21st amino acid used in ribosome-mediated protein synthesis – is incorporated in at least 25 specific, genetically determined
human selenoproteins, many of which have only recently been discovered. Restoration of normal selenoprotein levels may be
– apart from direct supranutritional effects – one possible explanation for the effects of selenium supplements. In this review
we provide a brief but up-to-date overview of what is currently known about these 25 acknowledged human selenoproteins and
their synthesis.
Received 30 March 2005; received after revision 4 July 2005; accepted 13 July 2005 相似文献
4.
Proinsulin C-peptide and its analogues induce intracellular Ca2+ increases in human renal tubular cells 总被引:3,自引:0,他引:3
Shafqat J Juntti-Berggren L Zhong Z Ekberg K Köhler M Berggren PO Johansson J Wahren J Jörnvall H 《Cellular and molecular life sciences : CMLS》2002,59(7):1185-1189
Based on the findings that proinsulin C-peptide binds specifically to cell membranes, we investigated the effects of C-peptide
and related molecules on the intracellular Ca2+ concentration ([Ca2+]i) in human renal tubular cells using the indicator fura-2/AM. The results show that human C-peptide and its C-terminal pentapeptide
(positions 27–31, EGSLQ), but not the des (27–31) C-peptide or randomly scrambled C-peptide, elicit a transient increase in
[Ca2+]i. Rat C-peptide and rat C-terminal pentapeptide also induce a [Ca2+]i response in human tubular cells, while a human pentapeptide analogue with Ala at position 1 gives no [Ca2+]i response, and those with Ala at positions 2–5 induce responses with different amplitudes. These results define a species
cross-reactivity for C-peptide and demonstrate the importance of Glu at position 1 of the pentapeptide. Preincubation of cells
with pertussis toxin abolishes the effect on [Ca2+]i by both C-peptide and the pentapeptide. These results are compatible with previous data on C-peptide binding to cells and
activation of Na+,K+ATPase. Combined, all data show that C-peptide is a bioactive peptide and suggest that it elicits changes in [Ca2+]i via G-protein-coupled pathways, giving downstream enzyme effects.
Received 13 May 2002; accepted 16 May 2002 相似文献
5.
Andrea Venerando Oriano Marin Giorgio Cozza Victor H. Bustos Stefania Sarno Lorenzo Alberto Pinna 《Cellular and molecular life sciences : CMLS》2010,67(7):1105-1118
The ability of three isoforms of protein kinase CK1 (α, γ1, and δ) to phosphorylate the N-terminal region of p53 has been assessed using either recombinant p53 or a synthetic peptide
reproducing its 1–28 sequence. Both substrates are readily phosphoylated by CK1δ and CK1α, but not by the γ isoform. Affinity
of full size p53 for CK1 is 3 orders of magnitude higher than that of its N-terminal peptide (K
m 0.82 μM vs 1.51 mM). The preferred target is S20, whose phosphorylation critically relies on E17, while S6 is unaffected
despite displaying the same consensus (E-x-x-S). Our data support the concept that non-primed phosphorylation of p53 by CK1
is an isoform-specific reaction preferentially affecting S20 by a mechanism which is grounded both on a local consensus and
on a remote docking site mapped to the K221RQK224 loop according to modeling and mutational analysis. 相似文献
6.
4-Hydroxynonenal-modified amyloid-beta peptide inhibits the proteasome: possible importance in Alzheimer's disease 总被引:3,自引:0,他引:3
Shringarpure R Grune T Sitte N Davies KJ 《Cellular and molecular life sciences : CMLS》2000,57(12):1802-1809
The amyloid β-peptide (Aβ) is a 4-kDa species derived from the amyloid precursor protein, which accumulates in the brains of patients with Alzheimer’s
disease. Although we lack full understanding of the etiology and pathogenesis of selective neuron death, considerable data
do imply roles for both the toxic Aβ and increased oxidative stress. Another significant observation is the accumulation of abnormal, ubiquitin-conjugated proteins
in affected neurons, suggesting dysfunction of the proteasome proteolytic system in these cells. Recent reports have indicated
that Aβ can bind and inhibit the proteasome, the major cytoslic protease for degrading damaged and ubiquitin-conjugated proteins.
Earlier results from our laboratory showed that moderately oxidized proteins are preferentially recognized and degraded by
the proteasome; however, severely oxidized proteins cannot be easily degraded and, instead, inhibit the proteasome. We hypothesized
that oxidatively modified Aβ might have a stronger (or weaker) inhibitory effect on the proteasome than does native Aβ. We therefore also investigated the proteasome inhibitory action of Aβ
1–40 (a peptide comprising the first 40 residues of Aβ) modified by the intracellular oxidant hydrogen peroxide, and by the lipid peroxidation product 4-hydroxynonenal (HNE). H2O2 modification of Aβ
1–40 generates a progressively poorer inhibitor of the purified human 20S proteasome. In contrast, HNE modification of Aβ
1–40 generates a progressively more selective and efficient inhibitor of the degradation of fluorogenic peptides and oxidized
protein substrates by human 20S proteasome. This interaction may contribute to certain pathological manifestations of Alzheimer’s
disease
Received 26 September 2000; accepted 26 September 2000 相似文献
7.
Terhi Vihervaara Riikka-Liisa Uronen Gerd Wohlfahrt Ingemar Björkhem Elina Ikonen Vesa M. Olkkonen 《Cellular and molecular life sciences : CMLS》2011,68(3):537-551
ORP1L is an oxysterol binding homologue that regulates late endosome (LE) positioning. We show that ORP1L binds several oxysterols
and cholesterol, and characterize a mutant, ORP1L Δ560–563, defective in oxysterol binding. While wild-type ORP1L clusters
LE, ORP1L Δ560–563 induces LE scattering, which is reversed by disruption of the endoplasmic reticulum (ER) targeting FFAT
motif, suggesting that it is due to enhanced LE–ER interactions. Endosome motility is reduced upon overexpression of ORP1L.
Both wild-type ORP1L and the Δ560–563 mutant induce the recruitment of both dynactin and kinesin-2 on LE. Most of the LE decorated
by overexpressed ORP1L fail to accept endocytosed dextran or EGF, and the transfected cells display defective degradation
of internalized EGF. ORP1L silencing in macrophage foam cells enhances endosome motility and results in inhibition of [3H]cholesterol efflux to apolipoprotein A-I. These data demonstrate that LE motility and functions in both protein and lipid
transport are regulated by ORP1L. 相似文献
8.
Bhavani S. Sahu Parshuram J. Sonawane Nitish R. Mahapatra 《Cellular and molecular life sciences : CMLS》2010,67(6):861-874
Chromogranin A (CHGA) is ubiquitously expressed in secretory cells of the endocrine, neuroendocrine, and neuronal tissues.
Although this protein has long been known as a marker for neuroendocrine tumors, its role in cardiovascular disease states
including essential hypertension (EH) has only recently been recognized. It acts as a prohormone giving rise to bioactive
peptides such as vasostatin-I (human CHGA1–76) and catestatin (human CHGA352–372) that exhibit several cardiovascular regulatory functions. CHGA is over-expressed but catestatin is diminished in EH. Moreover,
genetic variants in the promoter, catestatin, and 3′-untranslated regions of the human CHGA gene alter autonomic activity and blood pressure. Consistent with these findings, targeted ablation of this gene causes severe
arterial hypertension and ventricular hypertrophy in mice. Transgenic expression of the human CHGA gene or exogenous administration of catestatin restores blood pressure in these mice. Thus, the accumulated evidence establishes
CHGA as a novel susceptibility gene for EH. 相似文献
9.
Potassium and sodium transport in non-animal cells: the Trk/Ktr/HKT transporter family 总被引:1,自引:1,他引:0
C. Corratgé-Faillie M. Jabnoune S. Zimmermann A.-A. Véry C. Fizames H. Sentenac 《Cellular and molecular life sciences : CMLS》2010,67(15):2511-2532
Bacterial Trk and Ktr, fungal Trk and plant HKT form a family of membrane transporters permeable to K+ and/or Na+ and characterized by a common structure probably derived from an ancestral K+ channel subunit. This transporter family, specific of non-animal cells, displays a large diversity in terms of ionic permeability,
affinity and energetic coupling (H+–K+ or Na+–K+ symport, K+ or Na+ uniport), which might reflect a high need for adaptation in organisms living in fluctuating or dilute environments. Trk/Ktr/HKT
transporters are involved in diverse functions, from K+ or Na+ uptake to membrane potential control, adaptation to osmotic or salt stress, or Na+ recirculation from shoots to roots in plants. Structural analyses of bacterial Ktr point to multimeric structures physically
interacting with regulatory subunits. Elucidation of Trk/Ktr/HKT protein structures along with characterization of mutated
transporters could highlight functional and evolutionary relationships between ion channels and transporters displaying channel-like
features. 相似文献
10.
Gineitis A Treigyte G Savickiene J Shanbhag VP Stigbrand T 《Cellular and molecular life sciences : CMLS》1999,55(2):317-326
The two-dimensional electrophoretic patterns of nuclear proteins and their tyrosine phosphorylation were compared for HL-60
cells before and after differentiation induction to granulocytes by dimethyl sulfoxide, all-trans retinoic acid and N
6,O
2-dibutyryl adenosine 3′5′-cyclic monophosphate. Regardless of the inducer used, some nuclear proteins, which are tyrosine-phosphorylated
in proliferating HL-60 cells, undergo gradual dephosphorylation 12–72 h after induction of differentiation, followed by drastic
dephosphorylation during maturation to granulocytes. At least 13 nuclear proteins with a molecular mass of 35–110 kDa are
dephosphorylated, and 6 nuclear proteins undergo tyrosine phosphorylation. Analysis of the nuclear proteins differentially
extracted by salt and detergents indicates that changes in their tyrosine phosphorylation during the maturation stage of differentiating
granulocytes occur mainly in proteins which are abundant in nucleoplasm, chromatin and residual nuclear structures. The abundance
of these proteins, residing in the nuclear structures, and their long-term modification in phosphorylation during the maturation
stages of differentiation strongly suggest that tyrosine phosphorylation of these proteins is involved in reorganization of
the differentiating cell nucleus.
Received 21 September 1998; received after revision 24 November 1998; accepted 3 December 1998 相似文献
11.
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
12.
Gemma Olmos María I. Arenas Raquel Bienes María Jose Calzada Julián Aragonés Maria Laura Garcia-Bermejo Manuel O. Landazuri Javier Lucio-Cazaña 《Cellular and molecular life sciences : CMLS》2009,66(13):2167-2180
Hypoxia-inducible factor-1α (HIF-1α) protein is degraded under normoxia by its association to von Hippel-Lindau protein (pVHL)
and further proteasomal digestion. However, human renal cells HK-2 treated with 15-deoxy-Δ12,14-prostaglandin-J2 (15d-PGJ2) accumulate HIF-1α in normoxic conditions. Thus, we aimed to investigate the mechanism involved in this accumulation. We
found that 15d-PGJ2 induced an over-accumulation of HIF-1α in RCC4 cells, which lack pVHL and in HK-2 cells treated with inhibitors of the pVHL-proteasome
pathway. These results indicated that pVHL-proteasome-independent mechanisms are involved, and therefore we aimed to ascertain
them. We have identified a new lysosomal-dependent mechanism of HIF-1α degradation as a target for 15d-PGJ2 based on: (1) HIF-1α colocalized with the specific lysosomal marker Lamp-2a, (2) 15d-PGJ2 inhibited the activity of cathepsin B, a lysosomal protease, and (3) inhibition of lysosomal activity did not result in over-accumulation
of HIF-1α in 15d-PGJ2-treated cells. Therefore, expression of HIF-1α is also modulated by lysosomal degradation. 相似文献
13.
The Membrane Protein Data Bank (MPDB) is an online, searchable, relational database of structural and functional information
on integral, anchored and peripheral membrane proteins and peptides. Data originates from the Protein Data Bank and other
databases, and from the literature. Structures are based on X-ray and electron diffraction, nuclear magnetic resonance and
cryoelectron microscopy. The MPDB is searchable online by protein characteristic, structure determination method, crystallization
technique, detergent, temperature, pH, author, etc. Record entries are hyperlinked to the PDB and Pfam for viewing sequence,
three-dimensional structure and domain architecture, and for downloading coordinates. Links to PubMed are also provided. The
MPDB is updated weekly in parallel with the Protein Data Bank. Statistical analysis of MPDB records can be performed and viewed
online. A summary of the statistics as applied to entries in the MPDB is presented. The data suggest conditions appropriate
for crystallization trials with novel membrane proteins.
Received 3 August 2005; received after revision 18 September 2005; accepted 26 September 2005
This paper and the Membrane Protein Data Bank celebrate the 20th anniversary of the landmark paper in Nature (1985, 318: 618–624) describing the first ‘high-resolution’ three-dimensional structure of a membrane protein, the photosynthetic reaction
center from Rhodopseudomonas (Blastochloris) viridis. 相似文献
14.
Ahlsén M Carlsson-Skwirut C Jonsson AP Cederlund E Bergman T Bang P 《Cellular and molecular life sciences : CMLS》2007,64(14):1870-1880
Proteolytic cleavage of insulin-like growth factor (IGF) binding protein (IGFBP)-3 during pregnancy is likely to have both
IGF-dependent and -independent effects on maternal, placental and fetal growth and metabolism. A 30-kDa proteolytic IGFBP-3
fragment was isolated from third trimester pregnancy human serum and identified by N- and C-terminal amino acid sequence analysis
and mass spectrometry to correspond to residues 1–212 of the parent protein. This fragment is the dominating IGFBP-3 immunoreactive
species in pregnancy serum. The 30-kDa fragment was also detected in serum of non-pregnant women where it coexists with intact
IGFBP-3. Using biosensor technology, (1–212)IGFBP-3 was found to have 11-fold lower affinity for IGF-I compared to intact
IGFBP-3, while a 4-fold decrease in affinity was found for IGF-II. Tests with des(1–3)IGF-I suggest fast binding of IGF-I
to the N-terminal region of IGFBP-3 and similar affinity to a slow binding site in the C-terminal region.
Received 24 April 2007; received after revision 11 June 2007; accepted 13 June 2007 相似文献
15.
Sánchez-Margalet V González-Yanes C Santos-Alvarez J Najib S 《Cellular and molecular life sciences : CMLS》1999,55(1):142-147
Insulin action is initiated by binding to its cognate receptor, which then triggers multiple cellular responses by activating
different signaling pathways. There is evidence that insulin receptor signaling may involve G protein activation in different
target cells. We have studied the activation of G proteins in rat hepatoma (HTC) cells. We found that insulin stimulated binding
of guanosine 5′-O-(3-thiotriphosphate) (GTP-γ-35S) to plasma membrane proteins of HTC cells, in a dose-dependent manner. This effect was completely blocked by pertussis toxin
treatment of the membranes, suggesting the involvement of G proteins of the Gα
i/Gα
o family. The expression of these Gα proteins was checked by Western blotting. Next, we used blocking antibodies to sort out the specific Gα protein activated by insulin stimulation. Anti-Gα
il,2 antibodies completely prevented insulin-stimulated GTP binding, whereas anti-Gα
o,i3 did not modify this effect of insulin on GTP binding. Moreover, we found physical association of the insulin receptor with
Gα
i1,2 by copurification studies. These results further support the involvement of a pertussis toxin-sensitive G protein in insulin
receptor signaling and provides some evidence of specific association and activation of Gα
i1,2 protein by insulin. These findings suggest that Gα
i1,2 proteins might be involved in insulin action.
Received 23 September 1998; received after revision 23 November 1998; accepted 25 November 1998 相似文献
16.
Endoplasmic reticulum stress responses 总被引:7,自引:0,他引:7
Schröder M 《Cellular and molecular life sciences : CMLS》2008,65(6):862-894
In homeostasis, cellular processes are in a dynamic equilibrium. Perturbation of homeostasis causes stress. In this review
I summarize how perturbation of three major functions of the endoplasmic reticulum (ER) in eukaryotic cells–protein folding,
lipid and sterol biosynthesis, and storing intracellular Ca2+ – causes ER stress and activates signaling pathways collectively termed the unfolded protein response (UPR). I discuss how
the UPR reestablishes homeostasis, and summarize our current understanding of how the transition from protective to apoptotic
UPR signaling is controlled, and how the UPR induces inflammatory signaling.
Received 21 August 2007; received after revision 26 October 2007; accepted 29 October 2007 相似文献
17.
J. -P. Bargetzi 《Cellular and molecular life sciences : CMLS》1958,14(12):445-447
Summary Two closely related forms ofCoregonus from Lake Neuchatel were examined cytologically and biochemically, in order to ascertain the chromosome number and the DNA
content of haploid and diploid nuclei.Coregonus fera has 2N=78 ± 2 chromosomes, and a DNA content (diploid) of 5.8 × 10−9 mg;Coregonus macrophthalmus, 2N=78+ ± 3, DNA content of 6.1 × 10−9 mg. The difference between the two DNA constants is statistically significant. These results do not support the hypothesis
which postulates that polyploidy may be a determining factor in the speciation of these fishes.
相似文献
18.
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
19.
Muñoz U Bartolomé F Esteras N Bermejo-Pareja F Martín-Requero A 《Cellular and molecular life sciences : CMLS》2008,65(21):3507-3519
It has been proposed that neuroinflammation, among other factors, may trigger an aberrant neuronal cell cycle re-entry leading
to neuronal death. Cell cycle disturbances are also detectable in peripheral cells from Alzheimer’s disease (AD) patients.
We previously reported that the anti-inflammatory 15- deoxy-Δ12,14-prostaglandin J
2 (15d-PGJ
2) increased the cellular content of the cyclin-dependent kinase inhibitor p27, in lymphoblasts from AD patients. This work
aimed at elucidating the mechanisms of 15d-PGJ
2-induced p27 accumulation. Phosphorylation, half-life, and the nucleo-cytoplasmic traffic of p27 protein were altered by 15d-PGJ2
by mechanisms dependent on PI3K/Akt activity. 15d-PGJ
2 prevents the calmodulin-dependent Akt overactivation in AD lymphoblasts by blocking its binding to the 85-kDa regulatory
subunit of PI3K. These effects of 15d-PGJ
2 were not mimicked by 9,10-dihydro-15-deoxy-Δ12,14- prostaglandin J
2, suggesting that 15d-PGJ
2 acts independently of peroxisome proliferator-activated receptor γ activation and that the α,β-unsaturated carbonyl group
in the cyclopentenone ring of 15d-PGJ
2 is a requisite for the observed effects.
Received 14 July 2008; received after revision 2 September 2008; accepted 12 September 2008 相似文献