1,721,066 research outputs found
Polyamine Metabolism and Functions: Key Roles in Cellular Health and Disease
Full text linkThe polyamines putrescine, spermidine, and spermine are polycations ubiquitously present in cells, where they exert pleiotropic functions in cellular mechanisms like proliferation, protein synthesis (through the hypusination of the transcription factor EIF5a), redox balance, autophagy, and different forms of cell death [...
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
Structure-function relationships in the evolutionary framework of spermine oxidase
No full text""Spermine 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 signaling, nitric oxide synthesis and inhibition of immune responses. The oxidative products of spermine oxidase activity are spermidine, H2O2 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."
The analysis of rRNA sequence-structure in phylogenetics: An application to the family Pectinidae (Mollusca: Bivalvia)
No full textSeveral studies pointed out the relevance of integrating secondary structure information in sequence analysis and phylogenetics, both in terms of phylogenetic resolution and of marker suitability for phylogenetic reconstruction at higher taxonomic-rank. In this study we explore in a phylogenetic framework the primary and secondary structure information from nuclear (ITS2) and mitochondrial (16S) ribosomal DNA sequences from the Pectinidae, commonly known as scallops. Primary sequences were analysed under neighbour-joining, maximum parsimony, maximum likelihood, and Bayesian approaches. The individual RNA secondary structures were analysed alone and with primary sequences employing a combined model of sequence-structure evolution. The information from primary sequences and secondary structure of the ITS2 are concordant and provide good phylogenetic resolution, while the mitochondrial marker 16S fails to resolve the relationships between the major clades and shows a lack of structural signals. Our phylogenetic reconstruction provided evidence for the monophyly of the subfamily Pectininae and the tribes Aequipectinini and Pectinini while the subfamily Chlamydinae, although recovered in some analyses, did not receive good support. The secondary structure analysis of the derived pectinid ITS2 rRNA sequence revealed three striking differences between Pectininae and Chlamydinae subfamilies: (a) Chlamydinae ITS2 rRNA folding shows the typical four domains architecture, while the one of Pectininae only three; (b) the Pectinidae basal DI pairing shows a different sequence-structure consensus between Pectininae and Chlamydinae; (c) the Pectininae DIII domain holds a specific short secondary stem (Pec STEM). Furthermore, the scallop ITS2 rRNA folding analysis has shown the presence of a conserved sequence motif (invariably located on apical portion of the DIII domain) which emerges as a common feature across Bivalvia. The combined sequence-structure approach employed in this study, corroborates the deep significance of including the secondary structure information in phylogenetic analysis both as combined sequence-structure alignment as well as pointing out conserved elements of the RNA folding
Heterologous expression and characterization of mouse spermine oxidase RID A-4573-2009
No full textPolyamine oxidases are key enzymes responsible of the polyamine interconversion metabolism in animal cells. Recently, a novel enzyme belonging to this class of enzymes has been characterized for its capability to oxidize preferentially spermine and designated as spermine oxidase. This is a flavin adenine dinucleotide-containing enzyme, and it has been expressed both in vitro and in vivo systems. The primary structure of mouse spermine oxidase (mSMO) was deduced from a cDNA clone (Image Clone 264769) recovered by a data base search utilizing the human counterpart of polyamine oxidases, PAOh1. The open reading frame predicts a 555-amino acid protein with a calculated M-r of 61,852.30, which shows a 95.1% identity with PAOh1. To understand the biochemical properties of mSMO and its structure/function relationship, the mSMO cDNA has been subcloned and expressed in secreted and secreted-tagged forms into Escherichia coli BL21 DE3 cells. The recombinant enzyme shows an optimal pH value of 8.0 and is able to oxidize rapidly spermine to spermidine and 3-aminopropanal and fails to act upon spermidine and N-acetylpolyamines. The purified recombinant-tagged form enzyme (Mr. similar to68,000) has K. and k(cat) values of 90 mum and 4.5 s(-1), respectively, using spermine as substrate at pH 8.0. Molecular modeling of mSMO protein based on maize polyamine oxidase three-dimensional structure suggests that the general features of maize polyamine oxidase active site are conserved in mSMO
Ruolo dell'auxina nell'espressione del gene codificante la poliammino osidasi (PAO) in Zea Mays
No full textStructure-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
- …
