1,721,045 research outputs found
Structure-function relationships in the evolutionary framework of spermine oxidase
No full textSpermine oxidase is a FAD-dependent enzyme that specifically oxidizes spermine, and plays a central role in the highly regulated catabolism of polyamines in vertebrates. The spermine oxidase substrate is specifically spermine, a tetramine that plays mandatory roles in several cell functions, such as DNA synthesis, cellular proliferation, modulation of ion channels function, cellular signalling, nitric oxide synthesis and inhibition of immune responses. The oxidative products of spermine oxidase activity are spermidine, H 2O2 and the aldehyde 3-aminopropanal that spontaneously turns into acrolein. In this study the reconstruction of the phylogenetic relationships among spermine oxidase proteins from different vertebrate taxa allowed to infer their molecular evolutionary history, and assisted in elucidating the conservation of structural and functional properties of this enzyme family. The amino acid residues, which have been hypothesized or demonstrated to play a pivotal role in the enzymatic activity, and substrate specificity are here analysed to obtain a comprehensive and updated view of the structure-function relationships in the evolution of spermine oxidase. © 2013 Springer Science+Business Media New York
Polyamines metabolism and breast cancer: state of the art and perspectives
No full textBreast cancer (BC) is a common disease that generally occurs in women over the age of 50, and the risk is especially high for women over 60 years of age. One of the major BC therapeutic problems is that tumors initially responsive to chemotherapeutic approaches can progress to more aggressive forms poorly responsive to therapies. Polyamines (PAs) are small polycationic alkylamines, naturally occurring and essential for normal cell growth and development in eukaryotes. The intracellular concentration of PA is maintained within strongly controlled contents, while a dysregulation occurs in BC cells. Polyamines facilitate the interactions of transcription factors, such as estrogen receptors with their specific response element, and are involved in the proliferation of ER-negative and highly invasive BC tumor cells. Since PA metabolism has a critical role in cell death and proliferation, it represents a potential target for intervention in BC. The goal of this study was to perform a literature search reviewing the association between PA metabolism and BC, and the current evidence supporting the BC treatment targeting PA metabolism. We here describe in vitro and in vivo models, as well as the clinical trials that have been utilized to unveil the relationship between PA metabolism and BC. Polyamine pathway is still an important target for the development of BC chemotherapy via enzyme inhibitors. Furthermore, a recent promising strategy in breast anticancer therapy is to exploit the self-regulatory nature of PA metabolism using PA analogs to affect PA homeostasis. Nowadays, antineoplastic compounds targeting the PA pathway with novel mechanisms are of great interest and high social impact for BC chemotherapy
Cosmic rays and radiobiology in a Sino-Italian network strategy: First bilateral workshop COSMIC-RAD Foreword
No full textA New Transgenic Mouse Model for Studying the Neurotoxicity of Spermine Oxidase Dosage in the Response to Excitotoxic Injury
No full textSpermine oxidase is a FAD-containing enzyme involved in polyamines catabolism, selectively oxidizing spermine to produce H2O2, spermidine, and 3-aminopropanal. Spermine oxidase is highly expressed in the mouse brain and plays a key role in regulating the levels of spermine, which is involved in protein synthesis, cell division and cell growth. Spermine is normally released by neurons at synaptic sites where it exerts a neuromodulatory function, by specifically interacting with different types of ion channels, and with ionotropic glutamate receptors. In order to get an insight into the neurobiological roles of spermine oxidase and spermine, we have deregulated spermine oxidase gene expression producing and characterizing the transgenic mouse model JoSMOrec, conditionally overexpressing the enzyme in the neocortex. We have investigated the effects of spermine oxidase overexpression in the mouse neocortex by transcript accumulation, immunohistochemical analysis, enzymatic assays and polyamine content in young and aged animals. Transgenic JoSMOrec mice showed in the neocortex a higher H2O2 production in respect to Wild-Type controls, indicating an increase of oxidative stress due to SMO overexpression. Moreover, the response of transgenic mice to excitotoxic brain injury, induced by kainic acid injection, was evaluated by analysing the behavioural phenotype, the immunodistribution of neural cell populations, and the ultrastructural features of neocortical neurons. Spermine oxidase overexpression and the consequently altered polyamine levels in the neocortex affects the cytoarchitecture in the adult and aging brain, as well as after neurotoxic insult. It resulted that the transgenic JoSMOrec mouse line is more sensitive to KA than Wild-Type mice, indicating an important role of spermine oxidase during excitotoxicity. These results provide novel evidences of the complex and critical functions carried out by spermine oxidase and spermine in the mammalian brain. © 2013 Cervelli et al
Adaptive responses of heart and skeletal muscle to spermine oxidase overexpression: Evaluation of a new transgenic mouse model
No full textSpermine oxidase oxidizes spermine to produce H2O2, spermidine, and 3-aminopropanal. It is involved in cell drug response, apoptosis, and in the etiology of several pathologies, including cancer. Spermine oxidase is an important positive regulator of muscle gene expression and fiber size and, when repressed, leads to muscle atrophy. We have generated a transgenic mouse line overexpressing Smox gene in all organs, named Total-Smox. The spermine oxidase overexpression was revealed by β-Gal staining and reverse-transcriptase/PCR analysis, in all tissues analysed. Spermine oxidase activity resulted higher in Total-Smox than controls. Considering the important role of this enzyme in muscle physiology, we have focused our study on skeletal muscle and heart of Total-Smox mice by measuring redox status and oxidative damage. We assessed the redox homeostasis through the analysis of the reduced/oxidized glutathione ratio. Chronic H2O2 production induced by spermine oxidase overexpression leads to a cellular redox state imbalance in both tissues, although they show different redox adaptation. In skeletal muscle, catalase and glutathione S-transferase activities were significantly increased in Total-Smox mice compared to controls. In the heart, no differences were found in CAT activity level, while GST activity decreased compared to controls. The skeletal muscle showed a lower oxidative damage than in the heart, evaluated by lipid peroxidation and protein carbonylation. Altogether, our findings illustrate that skeletal muscle adapts more efficiently than heart to oxidative stress H2O2-induced. The Total-Smox line is a new genetic model useful to deepen our knowledge on the role of spermine oxidase in muscle atrophy and muscular pathological conditions like dystrophy. © 2016 Elsevier Inc
Inflammation, carcinogenesis and neurodegeneration studies in transgenic animal models for polyamine research
No full textNatural polyamines (PA) are cationic molecules affecting cell growth and proliferation. An association between increased polyamine biosynthesis and inflammation-induced carcinogenesis has been recognised. On the other hand, there are indications that inflammatory stimuli can up-regulate polyamine catabolism and that altered polyamine metabolism could affect pro- and anti-inflammatory cytokines. Since the polyamine content is strictly related to cell growth, a consistent number of evidences relate polyamine metabolism dysfunction with cancer. The increase of polyamine levels in malignant and proliferating cells attracted the interest of scientists during last decades, addressing polyamine depletion as a new strategy to inhibit carcinogenesis. Several studies suggest that PA also play an important role in neurodegeneration, but the mechanisms by which they participate in neuronal death are still unclear. Furthermore, the role of endogenous PA in normal brain functioning is yet to be elucidated. The consequences of an alteration of polyamine metabolism have also been approached in vivo with the use of transgenic animals overexpressing or devoid of some enzymes involved in polyamine metabolism. In the present work we review the experimental investigation carried out on inflammation, cancerogenesis and neurodegeneration using transgenic animals engineered as models for polyamine research. © 2013 Springer-Verlag
General features of the transcriptional response of mammalian cells to low- and high-LET irradiation
No full textTo understand the general features of the transcriptional response of mammalian cells to ionizing radiation we performed a meta-analysis of a transcriptomic dataset referring to 202 different irradiation conditions. Since there is a growing interest in the peculiarities of the response to high-LET versus low-LET irradiation, we enriched the dataset with high-LET conditions, Our results showed that the most general feature of the transcriptional response of mammalian cells to irradiation is the up-regulation CDKN1A which is universally observed in cancer and non-cancer cell lines and in highly proliferating tissues, such as skin, lymph node and blood. This induction does not require a wild-type P53 and is poorly radiation dose dependent. Moreover, it is observed at various times following both high- and low-LET irradiation. Among the genes mostly down-regulated by high-Let irradiation we found Pif1, a highly conserved protein that functions as DNA helicase and plays key roles in the protection of cells from DNA replication stress and DNA damage and in the maintenance of genome stability. � Accademia Nazionale dei Lincei 2014
Caves and other subsurface environments in the future exploration of Mars: The absence of natural background radiation as biology concern
No full textThe human deep space exploration focused on Mars, being the near eventual final destination. Mars surface habitation is considered a dangerous solution. Among others, radiation, micrometeorites and dust storms, are the major causes of risk for the human well-being during the mission. Caves on Mars can provide a natural shelter against these environmental hazards. Several practical applications address forward the use of caves as habitation opportunity. Within the caves, inflatable structures can be used, as opposed to the heavy structure surface buildings. For this reason, studies were taken to assess the possible areas for which caves could be used as human habitats as an alternative for an initial settlement of Mars. The results obtained not only suggest strong arguments for the use of caves, but also open questions for further quantification and understanding of current unknowns. In the present review,we focus on the hypothetical biological effects due to the cave shelter for natural background radiation that is of three orders of magnitude lower than Mars surface. Background radiation is the ubiquitous ionizing radiation that organisms experienced on the Earth, being present at the appearance of life on Earth. Nevertheless, both the effects of natural background radiation and its absence are not well known. We review the literature based on the effects of the absence of natural background to pursue a common scientific effort to gain scientific knowledge in this future deep space exploration scenario in a Sino-Italy cooperation, taking advantage of the JingPing cavern laboratory in the Sichuan region. © Accademia Nazionale dei Lincei 2013
Metodo per la determinazione dell'attivita' N1-N8 spermidina/spermina acetil transferasi (SSAT) mediante uso di inibitori dell'attivita' poliammino ossidasi (PAO)
No full textLa metallografia ottica nello studio di cricche e tensioni nei giunti saldati
No full textTo detect defects and residual stresses in a welded joint, is a fundamental aspect to determine the final product quality. Non-destructive tests highlight dimensions and positions of macroscopic defects but the best way to collect helpful data is the investigation of appropriate metallo graphic section. The selected investigation method to apply must be simple, accurate, reproducible and cheap both in time and money. Well consolidate sciences as optic and electronic metallography, allow, by a "sacrificial sample" to gain a big part of those fundamental information necessary to carry on with the research. To use and to tweak chemical etchings to obtain detailed observation of defective areas complete the aim. The goal of this work is the investigation, by tint metallography, of "hot tearing " and of hardening phenomena due to the residual stresses in artistic tin-bronzes during post-welding cooling processes. The selected chemical etching is a modified Klemm III which, producing a coloured micro structure, allows to recognize second phases or inclusions, hardening phenomena, residual stresses
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