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51.
Loss of CLPP alleviates mitochondrial cardiomyopathy without affecting the mammalian UPRmt
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Dominic Seiferling Karolina Szczepanowska Christina Becker Katharina Senft Steffen Hermans Priyanka Maiti Tim König Alexandra Kukat Aleksandra Trifunovic 《EMBO reports》2016,17(7):953-964
The mitochondrial matrix protease CLPP plays a central role in the activation of the mitochondrial unfolded protein response (UPRmt) in Caenorhabditis elegans. Far less is known about mammalian UPRmt signaling, although similar roles were assumed for central players, including CLPP. To better understand the mammalian UPRmt signaling, we deleted CLPP in hearts of DARS2‐deficient animals that show robust induction of UPRmt due to strong dysregulation of mitochondrial translation. Remarkably, our results clearly show that mammalian CLPP is neither required for, nor it regulates the UPRmt in mammals. Surprisingly, we demonstrate that a strong mitochondrial cardiomyopathy and diminished respiration due to DARS2 deficiency can be alleviated by the loss of CLPP, leading to an increased de novo synthesis of individual OXPHOS subunits. These results question our current understanding of the UPRmt signaling in mammals, while introducing CLPP as a possible novel target for therapeutic intervention in mitochondrial diseases. 相似文献
52.
Aleksandra Kładna Paweł Berczyński Irena Kruk Teresa Piechowska Hassan Y. Aboul‐Enein 《Luminescence》2016,31(6):1201-1206
Isoflavones genistein and daidzein are nonsteroidal phytoestrogens occurring mainly in soybean foods. These phytoestrogens possess estrogenic properties and show a variety of health benefits as anti‐inflammatory agents. However, the mechanism of their action has not been identified in detail. The aim of this study is to characterize the antioxidant powers of genistein, daidzein and daidzein metabolite–equol through their activities to scavenge superoxide anion radical (O?2?), hydroxyl radical (HO?), 2,2–diphenyl–1‐picrylhydrazyl radical (DPPH?) and hydrogen peroxide (H2O2) using chemiluminescence and spectrophotometry techniques. Potassium superoxide in dimethyl sulphoxide (DMSO) and 18‐crown‐6 ether were used as a source of O?2?. Hydroxyl radicals were produced using the Fenton reaction. In free radical assays, genistein had the IC50 values (an amount of antioxidant concentration required to decrease the initial radical concentration by 50%) 0.391 ± 0.012 mM for O?2?, 0.621 ± 0.028 mM for HO? and 1.89 ± 0.16 mM for DPPH?. The IC50 values for daidzein for these free radicals were 1.924 ± 0.011 mM, 0.702 ± 0.012 mM and 2.81 ± 0.03 mM, respectively. Equol was the most active the free radical scavenger with IC50 = 0.451 ± 0.018 mM for HO? and IC50 = 1.36 ± 0.11 mM for DPPH?. All tested compounds exerted a significant effect on the H2O2: IC50 = 18.1 ± 1.1 μM for genistein, IC50 = 2.1 ± 0.5 μM for daidzein, and IC50 = 1.06 ± 0.2 μM for equol. These findings show that genistein, daidzein and equol are effective free radical scavengers and possess high antioxidant power in vitro. Copyright © 2016 John Wiley & Sons, Ltd. 相似文献
53.
Genome Characteristics,Phylogeny and Varying Host Specificity of Polish Kra and Ros Isolates of Tomato torrado virus
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Budziszewska Marta Pospieszny Henryk Obrępalska‐Stęplowska Aleksandra 《Journal of Phytopathology》2016,164(4):281-285
The genome sequences of two Polish Kra and Ros isolates of Tomato torrado virus (ToTV) were determined and compared with data of previously described ToTV isolates and other Torradovirus members. Whole‐genome sequence comparisons revealed 97.0–99.6% nucleotide sequence identities and close relatedness, with other known ToTV isolates. The high homology between Kra, Ros and Wal'03 ToTVs is likely responsible for the similar symptoms observed on infected plants. However, the symptoms differed in intensity and various host specificity. We report that Kra ToTV caused a milder expression of symptoms on Solanum tuberosum than Wal'03. We hypothesize this may be a result of the significant variability observed within the 3′‐UTR of RNA1 of Kra as well as of Ros ToTV isolates. In the light of this fact, potato may be considered an indicator plant for distinguishing Kra and Wal'03 ToTV isolates. 相似文献
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Rodziewicz-Motowidło S Juszczyk P Kołodziejczyk AS Sikorska E Skwierawska A Oleszczuk M Grzonka Z 《Biopolymers》2007,87(1):23-39
The beta-amyloid (Abeta) is the major peptide constituent of neuritic plaques in Alzheimer's disease (AD) and its aggregation is believed to play a central role in the pathogenesis of the disease. Naturally occurring mutations resulting in changes in the Abeta sequence (pos. 21-23) are associated with familial AD-like diseases with extensive cerebrovascular pathology. It was proved that the mutations alter the aggregation ability of Abeta and its neurotoxicity. Among five mutations at positions 21-23 there are two mutations with distinct clinical characteristics and potentially distinct pathogenic mechanism-the Italian (E22K) and the Flemish (A21G) mutations. In our studies we have examined the structures of the 11-28 fragment of the Italian and Flemish Abeta variants. The fragment was chosen because it has been shown to be the most important for amyloid fibril formation. The detailed structure of both variants Abeta(11-28) was determined using CD, 2D NMR, and molecular dynamics techniques under water-SDS micelle conditions. The NMR analysis revealed two distinct sets of proton resonances for the peptides. The studies of both peptides pointed out the existence of well-defined alpha-helical conformation in the Italian mutant, whereas the Flemish was found to be unstructured with the possibility of a bent structure in the central part of the peptide. 相似文献
58.
Polarity of response to transforming growth factor-beta1 in proximal tubular epithelial cells is regulated by beta-catenin 总被引:1,自引:0,他引:1
Zhang M Lee CH Luo DD Krupa A Fraser D Phillips A 《The Journal of biological chemistry》2007,282(39):28639-28647
Transforming growth factor-beta1 (TGF-beta1)-mediated loss of proximal tubular epithelial cell-cell interaction is regulated in a polarized fashion. The aim of this study was to further explore the polarity of the TGF-beta1 response and to determine the significance of R-Smad-beta-catenin association previously demonstrated to accompany adherens junction disassembly. Smad3 signaling response to TGF-beta1 was assessed by activity of the Smad3-responsive reporter gene construct (SBE)(4)-Lux and by immunoblotting for phospho-Smad proteins. Similar results were obtained with both methods. Apical application of TGF-beta1 led to increased Smad3 signaling compared with basolateral stimulation. Association of Smad proteins with beta-catenin was greater following basolateral TGFbeta-1 stimulation, as was the expression of cytoplasmic Triton-soluble beta-catenin. Inhibition of beta-catenin expression by small interfering RNA augmented Smad3 signaling. Lithium chloride, a GSK-3 inhibitor, increased expression of beta-catenin and attenuated TGF-beta1-dependent Smad3 signaling. Lithium chloride did not influence degradation of Smad3 but resulted in decreased nuclear translocation. Smad2 activation as assessed by Western blot analysis and activity of the Smad2-responsive reporter constructs ARE/MF1 was also greater following apical as compared with basolateral TGFbeta-1 stimulation, suggesting that this is a generally applicable mechanism for the regulation of TGF-beta1-dependent R-Smads. Caco-2 cells are a colonic carcinoma cell line, with known resistance to the anti-proliferative effects of TGF-beta1 and increased expression of beta-catenin. We used this cell line to address the general applicability of our observations. Inhibition of beta-catenin in this cell line by small interfering RNA resulted in increased TGF-beta1-dependent Smad3 phosphorylation and restoration of TGF-beta1 anti-proliferative effects. 相似文献
59.
Hideyuki Yoshida Caleb A. Lareau Ricardo N. Ramirez Samuel A. Rose Barbara Maier Aleksandra Wroblewska Fiona Desland Aleksey Chudnovskiy Arthur Mortha Claudia Dominguez Julie Tellier Edy Kim Dan Dwyer Susan Shinton Tsukasa Nabekura YiLin Qi Bingfei Yu Michelle Robinette Christophe Benoist 《Cell》2019,176(4):897-912.e20
60.
We analysed 16 populations of Dactylorhiza majalis subsp. majalis from northern Poland, simultaneously utilizing both morphological and molecular data. Genetic differentiation was examined using five microsatellite loci, and morphological variation was assessed for 23 characters. At the species level, our results showed a moderate level of genetic diversity (A = 6.00; Ae = 1.86; Ho = 0.387; FIS = 0.139) which varied between the studied populations (A = 2.60–4.20; Ae = 1.68–2.39; Ho = 0.270–0.523; FIS = ?0.064–0.355). A significant excess of homozygotes was detected in five population, while excess of heterozygotes was observed in four populations, but the latter values were statistically insignificant. Moderate, but clear between population genetic differentiation was found (FST = 0.101; p < 0.001). Considering pairwise‐FST and number of migrants among populations, we recognized three population groups (I, II, III), where the first could be further divided into two subgroups (Ia, Ib). These three groups differed with respect to gene flow values (Nm = 0.39–1.12). The highest number of migrants per generation was noticed among populations of subgroup Ia (8.58), indicative of a central panmictic population with free gene flow surrounded by peripatric local populations (Ib) with more limited gene flow. Geographic isolation, habitat fragmentation and limited seed dispersal are inferred to have caused limitations to gene flow among the three indicated population groups. There was a significant correlation between the morphological and genetic distance matrices. A weak but significant pattern of isolation by distance was also observed (r = 0.351; p < 0.05). 相似文献