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111.
Christopher Minteer Marco Morselli Margarita Meer Jian Cao Albert HigginsChen Sabine M. Lang Matteo Pellegrini Qin Yan Morgan
E. Levine 《Aging cell》2022,21(2)
Aging is associated with dramatic changes to DNA methylation (DNAm), although the causes and consequences of such alterations are unknown. Our ability to experimentally uncover mechanisms of epigenetic aging will be greatly enhanced by our ability to study and manipulate these changes using in vitro models. However, it remains unclear whether the changes elicited by cells in culture can serve as a model of what is observed in aging tissues in vivo. To test this, we serially passaged mouse embryonic fibroblasts (MEFs) and assessed changes in DNAm at each time point via reduced representation bisulfite sequencing. By developing a measure that tracked cellular aging in vitro, we tested whether it tracked physiological aging in various mouse tissues and whether anti‐aging interventions modulate this measure. Our measure, termed CultureAGE, was shown to strongly increase with age when examined in multiple tissues (liver, lung, kidney, blood, and adipose). As a control, we confirmed that the measure was not a marker of cellular senescence, suggesting that it reflects a distinct yet progressive cellular aging phenomena that can be induced in vitro. Furthermore, we demonstrated slower epigenetic aging in animals undergoing caloric restriction and a resetting of our measure in lung and kidney fibroblasts when re‐programmed to iPSCs. Enrichment and clustering analysis implicated EED and Polycomb group (PcG) factors as potentially important chromatin regulators in translational culture aging phenotypes. Overall, this study supports the concept that physiologically relevant aging changes can be induced in vitro and used to uncover mechanistic insights into epigenetic aging. 相似文献
112.
Lennis Beatriz Ordua-Castillo Jorge Eduardo del-Río-Robles Irving García-Jimnez Csar Zavala-Barrera Yarely Mabell Beltrn-Navarro Joseline Janai Hidalgo-Moyle Iliana Ramírez-Rangel Marco A. Hernndez-Bedolla Alma P. Reyes-Ibarra Margarita Valadez-Snchez Jos Vzquez-Prado Guadalupe Reyes-Cruz 《Journal of cell communication and signaling》2022,16(2):239
Calcium sensing receptor, a pleiotropic G protein coupled receptor, activates secretory pathways in cancer cells and putatively exacerbates their metastatic behavior. Here, we show that various CaSR mutants, identified in breast cancer patients, differ in their ability to stimulate Rac, a small Rho GTPase linked to cytoskeletal reorganization and cell protrusion, but are similarly active on the mitogenic ERK pathway. To investigate how CaSR activates Rac and drives cell migration, we used invasive MDA-MB-231 breast cancer cells. We revealed, by pharmacological and knockdown strategies, that CaSR activates Rac and cell migration via the Gβγ-PI3K-mTORC2 pathway. These findings further support current efforts to validate CaSR as a relevant therapeutic target in metastatic cancer.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12079-021-00662-y. 相似文献
113.
Margarita Kirkova Elina Tzvetanova Stefani Vircheva Rositsa Zamfirova Beata Grygier Marta Kubera 《Cell biochemistry and function》2010,28(6):497-502
In vivo effects of the antidepressant fluoxetine on spleen antioxidant status of C57BL/6 mice were studied using a melanoma experimental model. After a 14‐day treatment with fluoxetine (10 mg kg?1 day?1, i.p.), the endogenous antioxidant non‐enzyme (glutathione) and enzyme (superoxide dismutase (SOD) and glutathione peroxidase (GPx)) defense systems in spleen of healthy animals were not changed; the lipid peroxidation (LP) was also unchanged. When B16F10 melanoma cells were introduced in C57BL/6 mice 2 h before fluoxetine treatment, a drug‐protective effect against the melanoma‐induced oxidative changes (increased LP and decreased total glutathione (GSH)‐level, as well as antioxidant enzyme activities) in spleen was observed. Fluoxetine dose‐dependently reduced the amounts of free oxygen radicals (hydroxyl and superoxide anion radicals), generated in chemical systems. Taken together, the present results suggest that fluoxetine, acting as antioxidant, prevents from melanoma‐induced oxidative changes in mice spleen. Copyright © 2010 John Wiley & Sons, Ltd. 相似文献
114.
The Old World sparrows (genus Passer) phylogeography and their relative abundance of nuclear mtDNA pseudogenes 总被引:2,自引:0,他引:2
Allende LM Rubio I Ruíz-Del-Valle V Guillén J Martínez-Laso J Lowy E Varela P Zamora J Arnaiz-Villena A 《Journal of molecular evolution》2001,53(2):144-154
The phylogenetic relationships of genus Passer (Old World sparrows) have been studied with species covering their complete world living range. Mitochondrial (mt) cyt b
genes and pseudogenes have been analyzed, the latter being strikingly abundant in genus Passer compared with other studied songbirds. The significance of these Passer pseudogenes is presently unclear. The mechanisms by which mt cyt b genes become pseudogenes after nuclear translocation are
discussed together with their mode of evolution, i.e., transition/transversion mitochondrial ratio is decreased in the nucleus,
as is the constraint for variability at the three codon positions. However, the skewed base composition according to codon
position (in 1st position the percentage is very similar for the four bases, in 2nd position there are fewer percentage of A and G and more percentage of T, and in 3rd codon position fewer percentage of G and T and is very rich in A and C) is maintained in the translocated nuclear pseudogenes.
Different nuclear internal mechanisms and/or selective pressures must exist for explaining this nuclear/mitochondrial differential
DNA base evolutive variability. Also, the phylogenetic usefulness of pseudogenes for defining relationships between closely
related lineages is stressed. The analyses suggest that the primitive genus Passer species comes from Africa, the Cape sparrow
being the oldest: P. hispaniolensis italiae is more likely conspecific to P. domesticus than to P. hispaniolensis. Also, Passer species are not included within weavers or Estrildinae or Emberizinae, as previously suggested. European and American Emberizinae sparrows are closely related to each other and seem to be the earliest species that radiated among the studied songbirds
(all in the Miocene Epoch).
Received: 29 November 2000 / Accepted: 22 March 2001 相似文献
115.
Genetic variation of Citrus tristeza virus isolates from California and Spain: evidence for mixed infections and recombination 总被引:5,自引:0,他引:5
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Rubio L Ayllón MA Kong P Fernández A Polek M Guerri J Moreno P Falk BW 《Journal of virology》2001,75(17):8054-8062
We examined the population structure and genetic variation of four genomic regions within and between 30 Citrus tristeza virus (CTV) isolates from Spain and California. Our analyses showed that most isolates contained a population of sequence variants, with one being predominant. Four isolates showed two major sequence variants in some genomic regions. The two major variants of three of these isolates showed very low nucleotide identity to each other but were very similar to those of other isolates, suggesting the possibility of mixed infections with two divergent isolates. Incongruencies of phylogenetic relationships in the different genomic regions and statistical analyses suggested that the genomes of some CTV sequence variants originated by recombination events between diverged sequence variants. No correlation was observed between geographic origin and nucleotide distance, and thus from a genetic view, the Spanish and Californian isolates analyzed here could be considered members of the same population. 相似文献
116.
Cathepsin B and other lysosomal cysteine proteinases are synthesized as inactive zymogens, which are converted to their mature forms by other proteases or by autocatalytic processing. Procathepsin B autoactivation was shown in vitro at pH 4.5 to be a bimolecular process with K(s) and k(cat) values of 2.1+/-0.9 microM and 0.12+/-0.02 s(-1)6.0. However, in the presence of 0.5 microg/ml of dextran sulfate, relatively rapid processing is observed even at pH 6.5 (t(1/2) approximately 90 min), suggesting that glycosaminoglycans are involved in in vivo processing of lysosomal cysteine proteases. 相似文献
117.
Immunohistochemical evidence of the presence of aromatase P450 in the rat hypophysis 总被引:1,自引:0,他引:1
Carretero J Vázquez G Blanco E Rubio M Santos M Martín-Clavijo A Torres JL Vázquez R 《Cell and tissue research》1999,295(3):419-423
In order to analyze whether aromatase is present in the hypophysis of adult rats, we have performed an immunohistochemical study in young adult male and female rats. Our study has revealed that the hypophysis of adult rats contains aromatase, although marked differences are found between the sexes. The hypophyses of male rats have cells immunoreactive for the enzyme, 34.40% of these hypophyseal cells showing reaction. By contrast, cells from female rats show very little reaction, only 0.84% of them being reactive. No significant differences in the percentage of immunoreactive cells between one phase and another are observed during the estrous cycle. Our results point to the immunohistochemical expression of aromatase in the hypophysis of adult rats and at the same time suggest that its expression is sex-dependent. The enzyme may therefore be involved in the regulation of adenohypophyseal cytology by androgens. 相似文献
118.
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120.
Various Escherichia coli promoters contain, in addition to the classical -35 and -10 hexamers, a third recognition element, named the UP element. Located upstream of the -35 box, UP elements stimulate promoter activity by forming a docking site for the C-terminal domain of the RNA polymerase alpha subunit (alphaCTD). Accumulating genetic, biochemical and structural information has provided a detailed picture on the molecular mechanism underlying UP element-dependent promoter stimulation in E.coli. However, far less is known about functional UP elements of Bacillus subtilis promoters. Here we analyse the strong early sigma(A)-RNA polymerase-dependent promoters C2, A2c and A2b of the lytic B.subtilis phage phi29. We demonstrate that the phage promoters contain functional UP elements although their contribution to promoter strength is very different. Moreover, we show that the UP element of the A2b promoter, being critical for its activity, is located further upstream of the -35 box than most E.coli UP elements. The importance of the UP elements for the phage promoters and how they relate to other UP elements are discussed. 相似文献