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91.
Zaharenko AJ Schiavon E Ferreira WA Lecchi M de Freitas JC Richardson M Wanke E 《Peptides》2012,34(1):158-167
During their evolution, animals have developed a set of cysteine-rich peptides capable of binding various extracellular sites of voltage-gated sodium channels (VGSC). Sea anemone toxins that target VGSCs delay their inactivation process, but little is known about their selectivities. Here we report the investigation of three native type 1 toxins (CGTX-II, δ-AITX-Bcg1a and δ-AITX-Bcg1b) purified from the venom of Bunodosoma cangicum. Both δ-AITX-Bcg1a and δ-AITX-Bcg1b toxins were fully sequenced. The three peptides were evaluated by patch-clamp technique among Nav1.1-1.7 isoforms expressed in mammalian cell lines, and their preferential targets are Na(v)1.5>1.6>1.1. We also evaluated the role of some supposedly critical residues in the toxins which would interact with the channels, and observed that some substitutions are not critical as expected. In addition, CGTX-II and δ-AITX-Bcg1a evoke different shifts in activation/inactivation Boltzmann curves in Nav1.1 and 1.6. Moreover, our results suggest that the interaction region between toxins and VGSCs is not restricted to the supposed site 3 (S3-S4 linker of domain IV), and this may be a consequence of distinct surface of contact of each peptide vs. targeted channel. Our data suggest that the contact surfaces of each peptide may be related to their surface charges, as CGTX-II is more positive than δ-AITX-Bcg1a and δ-AITX-Bcg1b. 相似文献
92.
Y Sato T Toyoda A Shimizu-Ibuka T Tamura K Kobayashi-Hattori T Nakamura S Arai K Mura 《Bioscience, biotechnology, and biochemistry》2012,76(7):1329-1333
Angiotensin I-converting enzyme (ACE) inhibitory activity was generated from elastin and collagen by hydrolyzing with thermolysin. The IC50 value of 531.6 μg/mL for ACE inhibition by the elastin hydrolysate was five times less than 2885.1 μg/mL by the collagen hydrolysate. We confirmed the antihypertensive activity of the elastin hydrolysate in vivo by feeding spontaneously hypertensive rats (male) on a diet containing 1% of the elastin hydrolysate for 9 weeks. About 4 week later, the systolic blood pressure of the rats in the elastin hydrolysate group had become significantly lower than that of the control group. We identified novel ACE inhibitory peptides, VGHyp, VVPG and VYPGG, in the elastin hydrolysate by using a protein sequencer and quadrupole linear ion trap (QIT)-LC/MS/MS. VYPGG had the highest IC50 value of 244 μM against ACE and may have potential use as a functional food. 相似文献
93.
Arese M Magnifico MC Mastronicola D Altieri F Grillo C Blanck TJ Sarti P 《IUBMB life》2012,64(3):251-258
A novel role of melatonin was unveiled, using immortalized human keratinocyte cells (HaCaT) as a model system. Within a time window compatible with its circadian rhythm, melatonin at nanomolar concentration raised both the expression level of the neuronal nitric oxide synthase mRNA and the nitric oxide oxidation products, nitrite and nitrate. On the same time scale, a depression of the mitochondrial membrane potential was detected together with a decrease of the oxidative phosphorylation efficiency, compensated by glycolysis as testified by an increased production of lactate. The melatonin concentration, ~ nmolar, inducing the bioenergetic effects and their time dependence, both suggest that the observed nitric oxide-induced mitochondrial changes might play a role in the metabolic pathways characterizing the circadian melatonin chemistry. 相似文献
94.
95.
96.
Pshenichnaya I Schouwey K Armaro M Larue L Knoepfler PS Eisenman RN Trumpp A Delmas V Beermann F 《Pigment cell & melanoma research》2012,25(3):312-325
c-Myc is involved in the control of diverse cellular processes and implicated in the maintenance of different tissues including the neural crest. Here, we report that c-Myc is particularly important for pigment cell development and homeostasis. Targeting c-Myc specifically in the melanocyte lineage using the floxed allele of c-Myc and Tyr::Cre transgenic mice results in a congenital gray hair phenotype. The gray coat color is associated with a reduced number of functional melanocytes in the hair bulb and melanocyte stem cells in the hair bulge. Importantly, the gray phenotype does not progress with time, suggesting that maintenance of the melanocyte through the hair cycle does not involve c-Myc function. In embryos, at E13.5, c-Myc-deficient melanocyte precursors are affected in proliferation in concordance with a reduction in numbers, showing that c-Myc is required for the proper melanocyte development. Interestingly, melanocytes from c-Myc-deficient mice display elevated levels of the c-Myc paralog N-Myc. Double deletion of c-Myc and N-Myc results in nearly complete loss of the residual pigmentation, indicating that N-Myc is capable of compensating for c-Myc loss of function in melanocytes. 相似文献
97.
Dopamine (DA) receptor and NMDA receptor (NMDAR) activation in the lateral (LA) nucleus of the amygdala plays a critical role in emotional processing. Several distinct mechanisms regulate the molecular cross-talk between DA receptors and NMDARs in different brain regions; however, the cellular mechanism through which DA modulates NMDARs in LA projection neurons has not been studied. Here, we investigated the effect of DA receptor activation on NMDAR currents in LA projection neurons recorded in amygdala slices obtained from young rats. We found that DA reduces NMDAR current amplitudes in an additive manner through the activation of both D1-like and D2-like receptors. The reduction of NMDAR current amplitudes by D1-like receptor activation is mediated by a protein-protein interaction between the D1R and the NMDAR, while the regulation of NMDAR activity by D2-like receptors is elicited through a G protein-dependent pathway controlled by D4R. The results of our investigation show for the first time a functional interplay between D1R and D4R that mediates coincident G protein-independent and dependent regulation of NMDARs. 相似文献
98.
Salmaso M Malacarne G Troggio M Faes G Stefanini M Grando MS Velasco R 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》2008,116(8):1129-1143
Grapevine molecular maps based on microsatellites, AFLP and RAPD markers are now available. SSRs are essential to allow cross-talks
between maps, thus upgrading any growing grapevine maps. In this work, single nucleotide polymorphisms (SNPs) were developed
from coding sequences and from unique BAC-end sequences, and nested in a SSR framework map of grapevine. Genes participating
to flavonoids metabolism and defence, and signal transduction pathways related genes were also considered. Primer pairs for
351 loci were developed from ESTs present on public databases and screened for polymorphism in the “Merzling” (a complex genotype
Freiburg 993–60 derived from multiple crosses also involving wild Vitis species) × Vitis vinifera (cv. Teroldego) cross population. In total 138 SNPs, 108 SSR markers and a phenotypic trait (berry colour) were mapped in
19 major linkage groups of the consensus map. In specific cases, ESTs with putatively related functions mapped near QTLs previously
identified for resistance and berry ripening. Genes related to anthocyanin metabolism mapped in different linkage groups.
A myb gene, which has been correlated with anthocyanin biosynthesis, cosegregated with berry colour on linkage group 2. The possibility
of associating candidate genes to known position of QTL is discussed for this plant.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.
Marzia Salmaso and Giulia Malacarne contributed equally to the present work. 相似文献
99.
Marchesi C Belicchi M Meregalli M Farini A Cattaneo A Parolini D Gavina M Porretti L D'Angelo MG Bresolin N Cossu G Torrente Y 《PloS one》2008,3(5):e2218
Background
Various prognostic serum and cellular markers have been identified for many diseases, such as cardiovascular diseases and tumor pathologies. Here we assessed whether the levels of certain stem cells may predict the progression of Duchenne muscular dystrophy (DMD).Methods and Findings
The levels of several subpopulations of circulating stem cells expressing the CD133 antigen were determined by flow cytometry in 70 DMD patients. The correlation between the levels and clinical status was assessed by statistical analysis. The median (±SD) age of the population was 10.66±3.81 (range 3 to 20 years). The levels of CD133+CXCR4+CD34- stem cells were significantly higher in DMD patients compared to healthy controls (mean±standard deviation: 17.38±1.38 vs. 11.0±1.70; P = 0.03) with a tendency towards decreased levels in older patients. Moreover, the levels of this subpopulation of cells correlated with the clinical condition. In a subgroup of 19 DMD patients after 24 months of follow-up, increased levels of CD133+CXCR4+CD34- cells was shown to be associated with a phenotype characterised by slower disease progression. The circulating CD133+CXCR4+CD34- cells in patients from different ages did not exhibit significant differences in their myogenic and endothelial in vitro differentiation capacity.Conclusions
Our results suggest that levels of CD133+CXCR4+CD34- could function as a new prognostic clinical marker for the progression of DMD. 相似文献100.
Cristina Mazzaccara Giuseppe Labruna Gennaro Cito Marzia Scarfò Mario De Felice Lucio Pastore Lucia Sacchetti 《PloS one》2008,3(11)