排序方式: 共有45条查询结果,搜索用时 15 毫秒
21.
P Perez-Martinez AI Perez-Caballero A Garcia-Rios EM Yubero-Serrano A Camargo MJ Gomez-Luna C Marin P Gomez-Luna A Dembinska-Kiec F Rodriguez-Cantalejo FJ Tinahones HM Roche F Perez-Jimenez J Lopez-Miranda J Delgado-Lista 《PloS one》2012,7(8):e43390
Background
TCF7L2 rs7903146 is an important genetic factor predicting type 2 diabetes (T2DM) which has also been linked to higher cardiovascular risk. To date, there is little information about the additional impact of this single nucleotide polymorphism (SNP) beyond glucose metabolism.Methodology/Principal Findings
We studied whether rs7903146 influenced postprandial lipid metabolism in three different populations (healthy young men, metabolic syndrome (MetS) patients and elderly persons). Eighty-eight healthy males were submitted to a single saturated fatty acid-rich test meal. Additionally, 110 middle-aged MetS patients and 20 healthy elderly persons (≥65 years) were submitted to three different dietary models followed by test meals. Minor allele homozygotes for rs7903146 showed a worse postprandial lipemia profile in young males, as seen by a lower HDL-cholesterol and Apo A1 concentration during the postprandial lipemia and a trend towards higher triglycerides (TG), than the other genotypes. In healthy elderly persons, carriers of the minor allele showed higher total cholesterol, LDL-cholesterol, Apo B and TG in the fasting state, and a higher postprandial area under the curve for total cholesterol, Apo B, small-triglyceride rich lipoprotein (TRL) cholesterol and small-(TRL) triglycerides. These results were accompanied by differential changes in adipokines. We did not observe any influence of rs7903146 on the postprandium of MetS patients.Conclusions/Significance
Healthy young males and elderly persons who are carriers of the mutant allele for rs7903146 have an impaired postprandial lipid metabolism that may be mediated by an alteration in adipokine regulation, and may be related to the higher cardiovascular risk observed in these persons.Trial Registration
ClinicalTrials.gov NCT00429195相似文献22.
Serine/threonine protein phosphatase 1 (PP1) regulates multiple cellular processes. Protein phosphorylation-dephosphorylation is largely altered during ischemia and subsequent reperfusion. The brain is particularly vulnerable to stress resulting from ischemia-reperfusion (IR), however, the acquisition of ischemic tolerance (IT) protects against IR stress. We studied PP1 complexes in response to IR stress and IT in brain using proteomic characterization of PP1 complexes in animal models of IR and IT. PP1alpha and PP1gamma were immunoprecipitated and resolved by 2-D. DIGE analysis detected 14 different PP1-interacting proteins that exhibited significant changes in their association with PP1alpha or PP1gamma. These proteins were identified by MALDI-TOF MS. Seven had the PP1-binding RVxF motif. IR altered the interaction of heat shock cognate 71 kDa-protein, creatine kinase B, and dopamine- and cAMP-regulated phosphoprotein 32 kDa (DARPP32) with both PP1alpha and PP1gamma, and the interaction of phosphodiesterase-6B, transitional ER ATPase, lamin-A, glucose-regulated 78 kDa-protein, dihydropyrimidinase-related protein-2, gamma-enolase, neurofilament-L, and ubiquitin ligase SIAH2 with PP1gamma. IT prevented most of the IR-induced effects. This study identifies novel PP1alpha- and PP1gamma-interacting proteins and reveals an in vivo modularity of PP1 holoenzymes in response to physiological ischemic stress. It supports a potential role of PP1 in IR stress and as a target of the endogenous protective mechanisms induced by IT. 相似文献
23.
Patrick Forterre Agnes Bergerat Purificacion Lopex-Garcia 《FEMS microbiology reviews》1996,18(2-3):237-248
Abstract: Hyperthermophilic archaea exhibit a unique pattern of DNA topoisomerase activities. They have a peculiar enzyme, reverse gyrase, which introduces positive superturns into DNA at the expense of ATP. This enzyme has been found in all hyperthermophiles tested so far (including Bacteria) but never in mesophiles. Reverse gyrases are formed by the association of a helicase-like domain and a 5'-type I DNA topoisomerase. These two domains might be located on the same polypeptide. However, in the methanogenic archaeon Methanopyrus kandleri , the topoisomerase domain is divided between two subunits. Besides reverse gyrase, Archaea contain other type I DNA topoisomerases; in particular, M. kandleri harbors the only known procaryotic 3'-type I DNA topoisomerase (Topo V). Hyperthermophilic archaea also exhibit specific type II DNA topoisomerases (Topo II), i.e. whereas mesophilic Bacteria have a Topo II that produces negative supercoiling (DNA gyrase), the Topo II from Sulfolobus and Pyrococcus lack gyrase activity and are the smallest enzymes of this type known so far. This peculiar pattern of DNA topoisomerases in hyperthermophilic archaea is paralleled by a unique DNA topology, i.e. whereas DNA isolated from Bacteria and Eucarya is negatively supercoiled, plasmidic DNA from hyperthermophilic archaea are from relaxed to positively supercoiled. The possible evolutionary implications of these findings are discussed in this review. We speculate that gyrase activity in mesophiles and reverse gyrase activity in hyperthermophiles might have originated in the course of procaryote evolution to balance the effect of temperature changes on DNA structure. 相似文献
24.
Localization of eukaryotic initiation factor 2 in neuron primary cultures and established cell lines
Maria V. T. Lobo F. Javier M. Alonso Susana Rodriguez Alberto Alcazar Elena Martin Francisco Munoz Rafael G-Santander Matilde Salinas Juan L. Fando 《Journal of molecular histology》1997,29(6):453-468
Eukaryotic initiation factor 2 (eIF-2) is a heterotrimeric protein with subunits α, β and γ that forms a ternary complex with
Met-tRNA and GTP. It promotes the binding of Met-tRNA to ribosomes and controls translational rates via phosphorylation/dephosphorylation
mechanisms. By means of immunofluorescence and post-embedding immunocytochemistry of intact cells and quantitative immunoblotting
of cell extracts, the cellular distribution of the initiation factor has been examined in primary neuronal cultures as well
as in two established cell lines: PC12 phaeochromocytoma cells and rat pituitary GH4C1 cells. Our results indicated that the
initiation factor is located not only in the cytoplasm but also in the nuclei of the cultured neurons and cell lines. In the
cytoplasm, immunocytochemical studies reveal that the factor is present mainly in those areas that are rich in ribosomes.
In the nucleus, the immunolabelling of eukaryotic initiation factor 2 verified the presence of gold particles in both nucleolar
and extranucleolar areas. The specific distribution of this factor on both sides of the nuclear envelope suggests that it
might have some nuclear-related function(s) besides its already known role in the control of translation 相似文献
25.
Moussard H Henneke G Moreira D Jouffe V López-García P Jeanthon C 《Applied and environmental microbiology》2006,72(3):2268-2271
We present a comparative analysis of two genome fragments isolated from a diverse and widely distributed group of uncultured euryarchaea from deep-sea hydrothermal vents. The optimal activity and thermostability of a DNA polymerase predicted in one fragment were close to that of the thermophilic archaeon Thermoplasma acidophilum, providing evidence for a thermophilic way of life of this group of uncultured archaea. 相似文献
26.
Kinetic mechanism of the Ca2+-dependent switch-on and switch-off of cardiac troponin in myofibrils 下载免费PDF全文
Solzin J Iorga B Sierakowski E Gomez Alcazar DP Ruess DF Kubacki T Zittrich S Blaudeck N Pfitzer G Stehle R 《Biophysical journal》2007,93(11):3917-3931
The kinetics of Ca2+-dependent conformational changes of human cardiac troponin (cTn) were studied on isolated cTn and within the sarcomeric environment of myofibrils. Human cTnC was selectively labeled on cysteine 84 with N-((2-(iodoacetoxy)ethyl)-N-methyl)amino-7-nitrobenz-2-oxa-1,3-diazole and reconstituted with cTnI and cTnT to the cTn complex, which was incorporated into guinea pig cardiac myofibrils. These exchanged myofibrils, or the isolated cTn, were rapidly mixed in a stopped-flow apparatus with different [Ca2+] or the Ca2+-buffer 1,2-Bis(2-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid to determine the kinetics of the switch-on or switch-off, respectively, of cTn. Activation of myofibrils with high [Ca2+] (pCa 4.6) induced a biphasic fluorescence increase with rate constants of >2000 s−1 and ∼330 s−1, respectively. At low [Ca2+] (pCa 6.6), the slower rate was reduced to ∼25 s−1, but was still ∼50-fold higher than the rate constant of Ca2+-induced myofibrillar force development measured in a mechanical setup. Decreasing [Ca2+] from pCa 5.0-7.9 induced a fluorescence decay with a rate constant of 39 s−1, which was approximately fivefold faster than force relaxation. Modeling the data indicates two sequentially coupled conformational changes of cTnC in myofibrils: 1), rapid Ca2+-binding (kB ≈ 120 μM−1 s−1) and dissociation (kD ≈ 550 s−1); and 2), slower switch-on (kon = 390s−1) and switch-off (koff = 36s−1) kinetics. At high [Ca2+], ∼90% of cTnC is switched on. Both switch-on and switch-off kinetics of incorporated cTn were around fourfold faster than those of isolated cTn. In conclusion, the switch kinetics of cTn are sensitively changed by its structural integration in the sarcomere and directly rate-limit neither cardiac myofibrillar contraction nor relaxation. 相似文献
27.
A Alcazar E Mendez J L-Fando M Salinas 《Biochemical and biophysical research communications》1988,153(1):313-320
The eukaryotic initiation factor 2 (eIF-2) from calf brain has been purified to homogeneity and free of endogenous kinase activity. Phosphorylation of eIF-2 factor has been examined with four different protein kinases. Casein kinase II, calcium/phospholipid-dependent protein kinase and cyclic AMP-dependent protein kinase from brain, phosphorylate the beta subunit of eIF-2, whilst hemin-controlled inhibitor phosphorylate the alpha subunit of the factor. According to the peptide maps obtained, the phosphorylation sites of the factor by the three beta kinases are specific and distinct. These data suggest a different regulation for the beta subunit through this modification. 相似文献
28.
In addition to the activity of heat shock protein 90 (Hsp90/HSPC) as a chaperone, some recent studies have reported expression
of Hsp90 at the cell surface in certain types of cancer and nervous system cells. We study the expression of Hsp90 at the
cell surface in human neuroblastoma (NB69) cells. Immunofluorescence experiments labeling with anti-Hsp90 antibodies on both
nonpermeabilized cells and live cells detected Hsp90 at the cell surface. Hsp90 was also identified in a membrane fraction
from subcellular fractionation. Cell-surface Hsp90 was significantly more expressed in undifferentiated proliferative spherical
neuroblastoma cells than in differentiated flattened cells. In addition, spherical cells were significantly more sensitive
to Hsp90 inhibitor 17-allylamino-17-demethoxygeldanamycin compared to flattened cells. This paper describes the first evidence
of cell-surface Hsp90 expression in a cancer cell line from nervous tissue and may indicate a novel target for anti-tumoral
agents. 相似文献
29.
Anne-Marie Callen Andr Adoutte Jose Manuel Andrew Anne Baroin-Tourancheau Marie-Hlne Br Purificacion Calvo Ruiz Jean-Claude Clrot Pilar Delgado Anne Fleury Rachel Jeanmaire-Wolf Vladimir Viklicky Eduardo Villalobo Nicolette Levilliers 《Biology of the cell / under the auspices of the European Cell Biology Organization》1994,81(2):95-119
Summary— Ciliates are very good models for studying post-translationally generated tubulin heterogeneity because they exhibit highly differentiated microtubular networks in combination with reduced genetic diversity. We have approached the analysis of tubulin heterogeneity in Paramecium through extensive isolation and characterization of monoclonal antibodies using various antigens and several immunization protocols. Eight monoclonal antibodies and 10 hybridoma supernatants were characterized by: i) immunoblotting on ciliate and pig brain tubulins as well as on peptide maps of Paramecium axonemal tubulin; ii) immunoblotting on ciliate tubulin fusion peptides generated in E coli, a procedure which allows in principle to discriminate antibodies that are directed against tubulin sequence (reactive on fusion peptides) from those directed against a post-translational epitope (non-reactive); and iii) immunofluorescence on Paramecium, 3T3 and PtK2 cells. Twelve antibodies labeled all microtubules in Paramecium cells and were found to be directed against tubulin primary sequences (nine of them being located in the α N-terminal domain, one in the β C-terminal one, and two in α and β central stretches). The remaining ones decorated only a specific subset of microtubules within the cell and were presumably directed against post-translational modifications. Among these, three antibodies are directed against an N-terminal acetylated epitope of α-tubulin whereas the epitopes of three other ones (TAP 952°, AXO 58 and AXO 49°) apparently correspond to still unidentified post-translational modifications, located in the C-terminal domain of both α- and β-tubulins. The AXO 49° specificity is similar to that of a previously described polyclonal serum raised against Paramecium axonemal tubulin [2]. The results are discussed in terms of identification and accessibility of the epitopes and immunogenicity of ciliate tubulin with reference to mammalian and ciliate tubulin sequences. 相似文献
30.
Tree genetic resources at risk in South America: A spatial threat assessment to prioritize populations for conservation 下载免费PDF全文
Maarten van Zonneveld Evert Thomas Nora P. Castañeda‐Álvarez Veerle Van Damme Carolina Alcazar Judy Loo Xavier Scheldeman 《Diversity & distributions》2018,24(6):718-729