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581.
de Castro LF Lozano D Portal-Núñez S Maycas M De la Fuente M Caeiro JR Esbrit P 《Journal of cellular physiology》2012,227(4):1752-1760
We here compared the changes induced by subcutaneous injection of PTHrP (1-36) or PTHrP (107-139) (80 μg/kg/day, 5 days/week for 4 or 8 weeks) in bone histology and bone remodeling factors, and in bone marrow cells (BMCs) ex vivo, in ovariectomized (OVX) mice. We also examined the osteogenic effects of these peptides in mouse mesenchymal C3H10T1/2 cells under oxidative stress condition in vitro, which recapitulates the effects of OVX. We confirmed that PTHrP (1-36) exerts bone anabolic actions, as assessed by bone histology and osteoblast differentiation markers in the long bones and plasma from OVX mice. PTHrP (107-139) was also efficient in stimulating several bone formation parameters, and it dramatically decreased bone resorption markers. Moreover, both PTHrP peptides modulate DKK-1 and Sost/sclerostin in osteoblast-like UMR-106 cells highly expressing these Wnt pathway inhibitors, related to their osteogenic action in this in vivo scenario. Administration of either PTHrP peptide improved osteogenic differentiation in BMCs from OVX mice ex vivo and in mouse mesenchymal C3H10T1/2 cells under oxidative stress condition in vitro. These data demonstrate that PTHrP (1-36) and PTHrP (107-139) can exert similar osteogenic effects in the appendicular skeleton of OVX mice. Our results suggest that these effects might occur in part by modulating the Wnt pathway. These findings lend credence to the notion that the osteogenic action of PTHrP (107-139) is likely a consequence of its anti-resorptive and anabolic features, and further support the usefulness of PTHrP (1-36) as a bone anabolic peptide in the setting of estrogen-depletion. 相似文献
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583.
Alexia Gómez Ines Sánchez‐Roman Jose Gomez Julia Cruces Ianire Mate Mónica Lopez‐Torres Alba Naudi Manuel Portero‐Otin Reinald Pamplona Monica De la Fuente Gustavo Barja 《Aging cell》2014,13(3):551-560
The membrane fatty acid unsaturation hypothesis of aging and longevity is experimentally tested for the first time in mammals. Lifelong treatment of mice with the β1‐blocker atenolol increased the amount of the extracellular‐signal‐regulated kinase signaling protein and successfully decreased one of the two traits appropriately correlating with animal longevity, the membrane fatty acid unsaturation degree of cardiac and skeletal muscle mitochondria, changing their lipid profile toward that present in much more longer‐lived mammals. This was mainly due to decreases in 22:6n‐3 and increases in 18:1n‐9 fatty acids. The atenolol treatment also lowered visceral adiposity (by 24%), decreased mitochondrial protein oxidative, glycoxidative, and lipoxidative damage in both organs, and lowered oxidative damage in heart mitochondrial DNA. Atenolol also improved various immune (chemotaxis and natural killer activities) and behavioral functions (equilibrium, motor coordination, and muscular vigor). It also totally or partially prevented the aging‐related detrimental changes observed in mitochondrial membrane unsaturation, protein oxidative modifications, and immune and behavioral functions, without changing longevity. The controls reached 3.93 years of age, a substantially higher maximum longevity than the best previously described for this strain (3.0 years). Side effects of the drug could have masked a likely lowering of the endogenous aging rate induced by the decrease in membrane fatty acid unsaturation. We conclude that it is atenolol that failed to increase longevity, and likely not the decrease in membrane unsaturation induced by the drug. 相似文献
584.
Cameron R. Cunningham Ameya Champhekar Michael V. Tullius Barbara Jane Dillon Anjie Zhen Justin Rafael de la Fuente Jonathan Herskovitz Heidi Elsaesser Laura M. Snell Elizabeth B. Wilson Juan Carlos de la Torre Scott G. Kitchen Marcus A. Horwitz Steven J. Bensinger Stephen T. Smale David G. Brooks 《PLoS pathogens》2016,12(1)
Persistent viral infections are simultaneously associated with chronic inflammation and highly potent immunosuppressive programs mediated by IL-10 and PDL1 that attenuate antiviral T cell responses. Inhibiting these suppressive signals enhances T cell function to control persistent infection; yet, the underlying signals and mechanisms that program immunosuppressive cell fates and functions are not well understood. Herein, we use lymphocytic choriomeningitis virus infection (LCMV) to demonstrate that the induction and functional programming of immunosuppressive dendritic cells (DCs) during viral persistence are separable mechanisms programmed by factors primarily considered pro-inflammatory. IFNγ first induces the de novo development of naive monocytes into DCs with immunosuppressive potential. Type I interferon (IFN-I) then directly targets these newly generated DCs to program their potent T cell immunosuppressive functions while simultaneously inhibiting conventional DCs with T cell stimulating capacity. These mechanisms of monocyte conversion are constant throughout persistent infection, establishing a system to continuously interpret and shape the immunologic environment. MyD88 signaling was required for the differentiation of suppressive DCs, whereas inhibition of stimulatory DCs was dependent on MAVS signaling, demonstrating a bifurcation in the pathogen recognition pathways that promote distinct elements of IFN-I mediated immunosuppression. Further, a similar suppressive DC origin and differentiation was also observed in Mycobacterium tuberculosis infection, HIV infection and cancer. Ultimately, targeting the underlying mechanisms that induce immunosuppression could simultaneously prevent multiple suppressive signals to further restore T cell function and control persistent infections. 相似文献
585.
Systems biology aims to study the properties of biological systems in terms of the properties of their molecular constituents. This occurs frequently by a process of mathematical modelling. The first step in this modelling process is to unravel the interaction structure of biological systems from experimental data. Previously, an algorithm for gene network inference from gene expression perturbation data was proposed. Here, the algorithm is extended by using regression with subset selection. The performance of the algorithm is extensively evaluated on a set of data produced with gene network models at different levels of simulated experimental noise. Regression with subset selection outperforms the previously stated matrix inverse approach in the presence of experimental noise. Furthermore, this regression approach enables us to deal with under-determination, that is, when not all genes are perturbed. The results on incomplete data sets show that the new method performs well at higher number of perturbations, even when noise levels are high. At lower number of perturbations, although still being able to recover the majority of the connections, less confidence can be placed in the recovered edges. 相似文献
586.
Margarita Villar Alessandra Torina Yolanda Nuñez Zorica Zivkovic Anabel Marina Angela Alongi Salvatore Scimeca Giuseppa La Barbera Santo Caracappa Jesús Vázquez José de la Fuente 《Proteome science》2010,8(1):1-14
Background
The UVB component of solar ultraviolet irradiation is one of the major risk factors for the development of skin cancer in humans. UVB exposure elicits an increased generation of reactive oxygen species (ROS), which are responsible for oxidative damage to proteins, DNA, RNA and lipids. In order to examine the biological impact of UVB irradiation on skin cells, we used a parallel proteomics approach to analyze the protein expression profile and to identify oxidatively modified proteins in normal human epithelial keratinocytes.Results
The expression levels of fifteen proteins - involved in maintaining the cytoskeleton integrity, removal of damaged proteins and heat shock response - were differentially regulated in UVB-exposed cells, indicating that an appropriate response is developed in order to counteract/neutralize the toxic effects of UVB-raised ROS. On the other side, the redox proteomics approach revealed that seven proteins - involved in cellular adhesion, cell-cell interaction and protein folding - were selectively oxidized.Conclusions
Despite a wide and well orchestrated cellular response, a relevant oxidation of specific proteins concomitantly occurs in UVB-irradiated human epithelial Keratinocytes. These modified (i.e. likely dysfunctional) proteins might result in cell homeostasis impairment and therefore eventually promote cellular degeneration, senescence or carcinogenesis. 相似文献587.
Rodríguez de la Fuente AO Alcocer-González JM Antonio Heredia-Rojas J Balderas-Candanosa I Rodríguez-Flores LE Rodríguez-Padilla C Taméz-Guerra RS 《Cell biology international》2009,33(3):419-423
We have evaluated the effect of 60 Hz sinusoidal magnetic fields (MF) at 8 and 8 μT on expression of the luciferase gene contained in a gene construct labelled as Electromagnetic Field-plasmid (pEMF). The vector included the hsp70 promotor containing the 3 nCTCTn sequences previously described for the induction of hsp70 expression by magnetic fields, as well as the reporter of the luciferase gene. We also replicated the study of Lin et al. [Lin H, Blank M, Rossol-Haseroth K, Goodman R. Regulating genes with electromagnetic response elements. J Cell Biochem 2001;81(1):143-48]. The pEMF plasmid was transfected into HeLa and BMK16 cell lines that were later exposed to either MF or thermal shock (TS). An increased luciferase expression was found in both the cells exposed to MF and TS compared with their control groups (P < 0.05). Furthermore, the combined effect of MF and TS was also analyzed. A synergistic effect between two factors was observed for this co-exposure condition in terms of luciferase gene expression. 相似文献
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589.
Polar Calcium Flux in Sunflower Hypocotyl Segments : II. The Effect of Segment Orientation, Growth, and Respiration 下载免费PDF全文
Calcium flux in sunflower (Helianthus annuus L. cv Russian mammoth) hypocotyl was measured with a Ca2+ electrode as the increase or decrease in Ca2+ in an aqueous solution (10 micromolar CaCl2) in contact with either the basal or apical end of 20 millimeter segments. Ca2+ efflux was significantly higher at the apical end compared with the basal end; this apparent polarity was maintained even when the segments were inverted. No significant difference was observed in the cation exchange capacity of apical and basal cell walls that could explain the difference in Ca2+ efflux at opposite ends of the hypocotyl segment. The presence of exogenous indoleacetic acid (IAA) in the segment medium resulted in the promotion of both Ca2+ efflux and segment elongation. However, osmotic inhibition of the IAA-induced elongation did not result in inhibiting the IAA-induced Ca2+ efflux. Ca2+ efflux was inhibited by cyanide. Lowering the temperature from 25°C also caused the gradual reduction of Ca2+ efflux; at 5°C the hypocotyl segments showed a net absorption of Ca2+ from the segment medium. These findings support the suggestion that: (a) the observed Ca2+ efflux in hypocotyl segments is probably the manifestation of the system which maintains the transmembrane Ca2+ gradient at the cellular level. (b) The acropetal polarity of Ca2+ efflux may be the result of the involvement of Ca2+ in the basipetal transport of IAA. 相似文献
590.