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121.
122.
Elena Grossini Kevin Bellofatto Serena Farruggio Lorenzo Sigaudo Patrizia Marotta Giulia Raina Veronica De Giuli David Mary Piero Pollesello Rosalba Minisini Mario Pirisi Giovanni Vacca 《PloS one》2015,10(4)
Background
Levosimendan protects rat liver against peroxidative injuries through mechanisms related to nitric oxide (NO) production and mitochondrial ATP-dependent K (mitoKATP) channels opening. However, whether levosimendan could modulate the cross-talk between apoptosis and autophagy in the liver is still a matter of debate. Thus, the aim of this study was to examine the role of levosimendan as a modulator of the apoptosis/autophagy interplay in liver cells subjected to peroxidation and the related involvement of NO and mitoKATP.Methods and Findings
In primary rat hepatocytes that have been subjected to oxidative stress, Western blot was performed to examine endothelial and inducible NO synthase isoforms (eNOS, iNOS) activation, apoptosis/autophagy and survival signalling detection in response to levosimendan. In addition, NO release, cell viability, mitochondrial membrane potential and mitochondrial permeability transition pore opening (MPTP) were examined through specific dyes. Some of those evaluations were also performed in human hepatic stellate cells (HSC). Pre-treatment of hepatocytes with levosimendan dose-dependently counteracted the injuries caused by oxidative stress and reduced NO release by modulating eNOS/iNOS activation. In hepatocytes, while the autophagic inhibition reduced the effects of levosimendan, after the pan-caspases inhibition, cell survival and autophagy in response to levosimendan were increased. Finally, all protective effects were prevented by both mitoKATP channels inhibition and NOS blocking. In HSC, levosimendan was able to modulate the oxidative balance and inhibit autophagy without improving cell viability and apoptosis.Conclusions
Levosimendan protects hepatocytes against oxidative injuries by autophagic-dependent inhibition of apoptosis and the activation of survival signalling. Such effects would involve mitoKATP channels opening and the modulation of NO release by the different NOS isoforms. In HSC, levosimendan would also play a role in cell activation and possible evolution toward fibrosis. These findings highlight the potential of levosimendan as a therapeutic agent for the treatment or prevention of liver ischemia/reperfusion injuries. 相似文献123.
Valentina Conti Anna Gandaglia Francesco Galli Mario Tirone Elisa Bellini Lara Campana Charlotte Kilstrup-Nielsen Patrizia Rovere-Querini Silvia Brunelli Nicoletta Landsberger 《PloS one》2015,10(6)
Rett syndrome (RTT) is an autism spectrum disorder mainly caused by mutations in the X-linked MECP2 gene and affecting roughly 1 out of 10.000 born girls. Symptoms range in severity and include stereotypical movement, lack of spoken language, seizures, ataxia and severe intellectual disability. Notably, muscle tone is generally abnormal in RTT girls and women and the Mecp2-null mouse model constitutively reflects this disease feature. We hypothesized that MeCP2 in muscle might physiologically contribute to its development and/or homeostasis, and conversely its defects in RTT might alter the tissue integrity or function. We show here that a disorganized architecture, with hypotrophic fibres and tissue fibrosis, characterizes skeletal muscles retrieved from Mecp2-null mice. Alterations of the IGF-1/Akt/mTOR pathway accompany the muscle phenotype. A conditional mouse model selectively depleted of Mecp2 in skeletal muscles is characterized by healthy muscles that are morphologically and molecularly indistinguishable from those of wild-type mice raising the possibility that hypotonia in RTT is mainly, if not exclusively, mediated by non-cell autonomous effects. Our results suggest that defects in paracrine/endocrine signaling and, in particular, in the GH/IGF axis appear as the major cause of the observed muscular defects. Remarkably, this is the first study describing the selective deletion of Mecp2 outside the brain. Similar future studies will permit to unambiguously define the direct impact of MeCP2 on tissue dysfunctions. 相似文献
124.
125.
Yeasts isolated from olive mill wastewaters from southern Italy: technological characterization and potential use for phenol removal 总被引:1,自引:0,他引:1
Milena Sinigaglia Nilde Di Benedetto Antonio Bevilacqua Maria Rosaria Corbo Angela Capece Patrizia Romano 《Applied microbiology and biotechnology》2010,87(6):2345-2354
Olive mill wastewater (OMW) samples from two traditional varieties (Peranzana and Ogliarola Garganica) of Apulian region (southern
Italy) and produced through continuous and traditional methods were microbiologically and chemically examined; thus, 104 yeasts
were isolated and selected for further analyses. The strains were identified as Candida boidinii, Pichia holstii, Pichia membranifaciens, and Saccharomyces cerevisiae and analyzed to assess their suitability to metabolize phenols. Based on phenol metabolism, 27 strains were selected and
inoculated into OMW aliquots to determine their ability to reduce phenols in vivo; then, five strains (identified with the
codes 682—C. boidinii and 625, 642, 647, and 941—P. holstii) were used as a cocktail in wastewaters for a final validation step. In this last experiment, the effects of the temperature
(10–30°C) and (NH4)2SO4 (0.0–6.0 g l−1) were studied through a central composite design approach, and the results highlighted that the cocktail was able to reduce
phenols by 40% at 10°C with 6.0 g l−1 of (NH4)2SO4 added. 相似文献
126.
127.
The year 2010 marks the 175th anniversary of Charles Darwin’s visit to the Galapagos Islands. A recent paper by J. C. Briggs, ‘Darwin’s biogeography’ (Journal of Biogeography, 2009, 36 , 1011–1017), summarizes Darwin’s contributions to the field of biogeography, stressing the importance of his natural history specimens. Here, we illustrate how a plant collected by Darwin during his visit to Floreana and not collected since can provide insights into dispersal to oceanic islands as well as extinction of island plants, based on ancient DNA from Darwin’s herbarium specimen. 相似文献
128.
129.
Grumati P Coletto L Sabatelli P Cescon M Angelin A Bertaggia E Blaauw B Urciuolo A Tiepolo T Merlini L Maraldi NM Bernardi P Sandri M Bonaldo P 《Nature medicine》2010,16(11):1313-1320
Autophagy is crucial in the turnover of cell components, and clearance of damaged organelles by the autophagic-lysosomal pathway is essential for tissue homeostasis. Defects of this degradative system have a role in various diseases, but little is known about autophagy in muscular dystrophies. We have previously found that muscular dystrophies linked to collagen VI deficiency show dysfunctional mitochondria and spontaneous apoptosis, leading to myofiber degeneration. Here we demonstrate that this persistence of abnormal organelles and apoptosis are caused by defective autophagy. Skeletal muscles of collagen VI-knockout (Col6a1(-/-)) mice had impaired autophagic flux, which matched the lower induction of beclin-1 and BCL-2/adenovirus E1B-interacting protein-3 (Bnip3) and the lack of autophagosomes after starvation. Forced activation of autophagy by genetic, dietary and pharmacological approaches restored myofiber survival and ameliorated the dystrophic phenotype of Col6a1(-/-) mice. Furthermore, muscle biopsies from subjects with Bethlem myopathy or Ullrich congenital muscular dystrophy had reduced protein amounts of beclin-1 and Bnip3. These findings indicate that defective activation of the autophagic machinery is pathogenic in some congenital muscular dystrophies. 相似文献
130.
De Rossi A Zanchetta M Vitone F Antonelli G Bagnarelli P Buonaguro L Capobianchi MR Clementi M Abbate I Canducci F Monachetti A Riva E Rozera G Scagnolari C Tagliamonte M Re MC;SIVIM 《The new microbiologica》2010,33(4):293-302
Despite the widespread use of molecular biology techniques, standardized methods for the measurement of HIV-1 proviral DNA are currently lacking and several discordant results are still present in different studies. To assess the clinical meaning of the proviral DNA load, a study group comprising seven different laboratories was set up to standardize a HIV-1 proviral DNA quantification method able to assess the DNA proviral load of the most relevant circulating HIV-1 subtypes. Reference samples (24 cellular samples infected with HIV-1 clade B, and 40 samples of peripheral blood mononuclear cells containing different concentrations of plasmids expressing different HIV-1 clades) were distributed and tested blindly. All laboratories employed hTERT gene as housekeeping gene and primers within the gag gene to quantify different HIV-1 clades. Inter-laboratory results did not differ statistically but showed only minor variations concerning HIV-1 DNA amounts and different HIV clades, with a good agreement among the laboratories participating in the study. Since test standardization represents a key step for future application in clinical practice, further studies of the patients' samples are in progress to establish the real meaning and utility of the proviral DNA load for clinical management of HIV-1 infected patients. 相似文献