1,721,058 research outputs found
Exploiting “oncogene addiction” and “premature senescence” to design novel therapeutic strategies for the treatment of cancer
No full textL’obiettivo principale del presente progetto è rappresentato dall'indagine del ruolo del segnale Ca2+ nei fenomeni di progressione e mantenimento tumorale promossi dall'oncogene RAS. Aumentare le nostre conoscenze circa il coinvolgimento del mitocondrio e della sua capacità d'interpretare segnali Ca2+ nel sostenere il fenotipo neoplastico. Far luce sui processi di OIS innescati dall'oncogene RAS, e capire come questi sono evasi nelle cellule tumorali. Lo scopo ultimo è d'identificare nuove vie di segnalazione intracellulare che potrebbero poi rappresentare nuovi bersagli terapeutici
A combination of miR501-5p and mTOR as molecular markers for the prognosis of renal carcinomas
No full text• Analisi dell’espressione del miR501-5p in campioni di tessuto di carcinoma renale e linee cellulari derivate da tumore renale.
• Caratterizzazione della funzione del miR501-5p nel carcinoma renale e identificazione di vie del segnale associate con la proliferazione cellulare, l’apoptosi, l’autofagia e modulate dal miR501-5p.
• Analisi del ruolo di mTOR e TP53 nel carcinoma renale in relazione con l’espressione del miR501-5p
Mitochondrial quality control machinery a role in the P. aeruginosa-triggered inflammatory response in Cystic Fibrosis
No full textPrincipal investigator, project FFC20/2015: The overall goal of this project is to broaden our knowledge
on role in vitro of mitochondrial quality control machinery to decode the pro-inflammatory signals
generated during P. aeruginosa infection in CF. Our attention is addressed to investigate about the
balance between xenophagy, mitophagy and UPRmt in P. aeruginosa-dependent inflammation response
and identify which mechanism fail during CF pathogenesis
Editorial: Oncogenic RAS-Dependent Reprogramming of Cellular Plasticity.
Full text linkNo abstract availlable
Ca2+ homeostasis of intracellular compartments: measurements using the jellyfish photo-protein aequorin
No full textThe development of molecular biology techniques (which enable the modification and expression of exogenous cDNA in heterologous cell types), has been responsible in recent years for the widespread use of protein probes by cell biologists, for the measurement of biological parameters. To this end, two main types of proteins are used, isolated from a wide variety of luminescent organisms.
The first group consists of chemiluminescent proteins. These are proteins that emit light, often associated to physiological parameters of interest, such as changes in ATP or Ca2+ concentration. Since mammalian cells do not possess endogenous lumiunescent molecules, the use of these proteins is normally associated to an excellent signal-to-noise ratio, as exemplified by aequorin, a photoprotein isolated from Aequorea victoria.
The second group consists of fluorescent proteins. Among these, Aequorea victoria's "Green Fluorescent Protein" (GFP) has attracted much attention, since its expression (or that of fusion products with proteins of interest) generates an intense signal, which enables complex phenomena (such as organelle structure and their dynamic changes, protein targeting, etc) to be followed in real time in living cells.
This review presents some of the results obtained using aequorin for studying intracellular Ca2+ homeostasis
Regulation of calcium fluxes by GPX8, a type-II transmembrane peroxidase enriched at the mitochondria-associated endoplasmic reticulum membrane
No full textGlutathione peroxidases (GPXs) are enzymes present in almost all organisms with the primary function of limiting peroxides accumulation. In mammals, two of the eight members (GPX7 and GPX8) reside in the endoplasmic reticulum (ER). A peculiar feature of GPX8 is the concomitant presence of a conserved N-terminal transmembrane domain (TMD) and a C-terminal KDEL-like motif for ER localization.
AIMS:
Investigating whether and how GPX8 impacts Ca2+ homeostasis and signaling.
RESULTS:
We show that GPX8 is enriched in mitochondria-associated membranes (MAM) and regulates Ca2+ storage and fluxes. Its levels correlate with [Ca2+]ER, and cytosolic and mitochondrial Ca2+ fluxes. GPX7, which lacks a TMD, does not share these properties. Deleting or replacing the GPX8 TMD with an unrelated N-terminal membrane integration sequence abolishes all effects on Ca2+ fluxes, whilst appending the GPX8 TMD to GPX7 transfers the Ca2+ regulating properties. Innovation and conclusion: The notion that the TMD of GPX8, in addition to its enzymatic activity, is essential for regulating Ca2+ dynamics, reveals a novel level of integration between redox related proteins and Ca2+ signaling/homeostasis
Control of mitochondrial functions by Pseudomonas aeruginosa in cystic fibrosis
No full textCystic fibrosis (CF) is a genetic disease characterized by mutations of cystic fibrosis transmembrane conductance regulator (CFTR) gene, which lead to a dysfunctional chloride and bicarbonate channel. Abnormal mucus viscosity, persistent infections and hyperinflammation that preferentially affect the airways, referred to the pathogenesis of CF lung disease. It has largely demonstrated that Pseudomonas aeruginosa (P. aeruginosa) represents the most important pathogen that affect CF patients, leading to worsen inflammation by stimulating pro-inflammatory mediators release and tissue destruction. The conversion to mucoid phenotype and formation of biofilms, together with the increased frequency of mutations, are only few changes that characterize the P. aeruginosa's evolution during CF lung chronic infection. Recently, mitochondria received increasing attention due to their involvement in inflammatory-related diseases, including in CF. Alteration of mitochondrial homeostasis is sufficient to stimulate immune response. Exogenous or endogenous stimuli that perturb mitochondrial activity are used by cells, which, through the mitochondrial stress, potentiate immunity programs. Studies show the relationship between mitochondria and CF, supporting the idea that mitochondrial dysfunction endorses the exacerbation of inflammatory responses in CF lung. In particular, evidences suggest that mitochondria in CF airway cells are more susceptible to P. aeruginosa infection, with consequent detrimental effects that lead to amplify the inflammatory signals. This review discusses the evolution of P. aeruginosa in relationship with the pathogenesis of CF, a fundamental step to establish chronic infection in CF lung disease. Specifically, we focus on the role of P. aeruginosa in the exacerbation of inflammatory response, by triggering mitochondria in CF
Calcium and mitochondria: mechanisms and functions of a troubled relationship.
No full textMitochondria promptly respond to Ca2+-mediated cell stimulations with a rapid accumulation of the cation into the matrix. In this article, we review (i) the basic principles of mitochondrial Ca2+ transport, (ii) the physiological/pathological role of mitochondrial Ca2+ uptake, (iii) the regulatory mechanisms that may operate in vivo, and (iv) the new targeted Ca2+ probes that allowed the “rediscovery” of these organelles in calcium signalling
Overview of CF lung pathophysiology
No full textDefects of the cystic fibrosis (CF) transmembrane conduc-tance regulator (CFTR) protein affect the homeostasis of chloride, bicarbonate, sodium, and water in the airway surface liquid, influencing the mucus composition and viscosity, which induces a severe condition of infection and inflammation along the whole life of CF patients. The introduction of CFTR mod-ulators, novel drugs directly intervening to rescue the function of CFTR protein, opens a new era of experimental research. The review summarizes the most recent advancements to understand the characteristics of the infective and inflamma -tory pathology of CF lungs
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