Search

In vista dell’avvio dei prossimi programmi europei e nazionali per la coesione 2021-2027, vengono proposte letture critiche di percorsi interpretativi, di “ricerca situata” e di progetto, legati a esperienze di sviluppo locale interne/esterne/prossime ai territori oggetto della Strategia Nazionale Aree Interne (SNAI), con un duplice obiettivo. Da un lato, supportare la costruzione di una mappatura dei tanti e diversi contesti “marginali” e “marginalizzati” del nostro paese, a partire dal riconoscimento delle loro potenzialità, risorse e capacità di reazione, e dalla messa a punto di strumenti qualitativi e quantitativi per la loro identificazione e indagine. Dall’altro, offrire un quadro ragionato delle politiche e delle progettualità (in corso o in programma), che ne evidenzi la portata (più o meno) innovativa nell’utilizzo di fondi straordinari, nelle pratiche di apprendimento all’interno delle istituzioni e tra gli attori territoriali, e nei processi di messa in rete di risorse, azioni e soggetti.

SIGNIFICANCE: Oxidative stress represents the common hallmark of pathological conditions associated with cardiovascular disease (CVD), including atherosclerosis, heart failure, hypertension, aging, diabetes, and other vascular system-related diseases. The sirtuin (SIRT) family, comprising seven proteins (SIRT1-SIRT7) sharing a highly conserved nicotinamide adenine dinucleotide (NAD+)-binding catalytic domain, attracted a great attention for the past few years as stress adaptor and epigenetic enzymes involved in the cellular events controlling aging-related disorder, cancer, and CVD. Recent Advances: Among sirtuins, SIRT1 and SIRT6 are the best characterized for their protective roles against inflammation, vascular aging, heart disease, and atherosclerotic plaque development. This latest role has been only recently unveiled for SIRT6. Of interest, in recent years, complex signaling networks controlled by SIRT1 and SIRT6 common to stress resistance, vascular aging, and CVD have emerged. CRITICAL ISSUES: We provide a comprehensive overview of recent developments on the molecular signaling pathways controlled by SIRT1 and SIRT6, two post-translational modifiers proven to be valuable tools to dampen inflammation and oxidative stress at the cardiovascular level. FUTURE DIRECTIONS: A deeper understanding of the epigenetic mechanisms through which SIRT1 and SIRT6 act in the signalings responsible for onset and development CVD is a prime scientific endeavor of the upcoming years. Multiple "omic" technologies will have widespread implications in understanding such mechanisms, speeding up the achievement of selective and efficient pharmacological modulation of sirtuins for future applications in the prevention and treatment of CVD. Antioxid. Redox Signal. 28, 711-732.

Résumé / Abstract Pectin methylesterase (PME) is present in plants and phytopathogenic microorganisms (bacteria and fungi) and is the first enzyme acting on pectin, which thereafter can be degraded by glycosidases. PME is present in plant as several isoforms, which are encoded by a multigene family (in Arabidopsis genome 67 PME-related genes have been identified). Regulation of plant PME occurs through the differential expression of isoforms in different tissues and developmental stages. In addition, the identification of a proteinaceous inhibitor (PMEI) specific for plant PMEs suggests the existence of a post-translational control mechanism. PMEI has been biochemically identified only in kiwi fruit. It has been recently shown that two gene sequences from Arabidopsis, cloned and expressed in a heterologous system, produce proteins having PMEI activity. The kiwi PMEI primary structure analysis has identified a structural motif consisting of 4 cysteines linked by disulfide bridge, first to second and third to fourth. This structural motif is also found in other plant proteins, the inhibitors of invertase, which have different target enzymes. PMEI has an interesting biotechnological application in food industry as inhibitor of endogenous PME, responsible for phase separation and cloud loss in fruit juice manufacturing.

A method for the determination of a low level of pectin methylesterase activity from vegetable products is described. The method is based on an affinity chromatography technique that employs a resin-bound pectin methylesterase inhibitor, purified from kiwi fruit, which selectively binds the pectin methylesterase. The resin has the capacity to concentrate the enzyme, allowing measurement of enzyme activities too low to be determined by commonly employed techniques and commensurate with those found in pasteurized food products. The enzyme is eluted from the resin at alkaline pH (9.5) and assayed by a pH-stat method. Depulped orange juices containing different amounts of pectin methylesterase were prepared and used to determine enzyme recovery. The results show a recovery of 90% with a standard deviation of 6.8%.

Rat mesangial cells stimulated with calcium ionophore A23187 and phagocytosis were shown to produce platelet-activating factor (PAF), a mediator of inflammation and endotoxic shock. In the study presented here, the cultured human mesangial but not epithelial cells synthetized PAF not only in response to calcium ionophore A23187 and phagocytosis of immunoglobulin G-coated latex beads, but also after stimulation with cytokines such as tumor necrosis factor-alpha and interleukin-1 beta. PAF synthetized after stimulation with A23187 and to a lesser extent with phagocytosis was partially released. In contrast, PAF synthesized by stimulation with tumor necrosis factor-alpha and interleukin-1 beta remained cell associated. Experiments with labeled precursors demonstrated that PAF was synthetized via the remodeling pathway that involves the activation of phospholipase A2 and of an acetyl-coenzymeA:2-lyso-PAF acetyltransferase. Synthetic inhibitors of serine proteases as well as plasma alpha 1-proteinase inhibitor inhibited the activation of phospholipase A2 detected as release of (14C) arachidonic acid and the activation of acetyl-CoA:2-lyso-PAF acetyltransferase at concentrations 100-fold lower than those present in plasma. This raises the question about the ability of mesangial cells to synthetize PAF in vivo. However, the inhibitory effect of plasma alpha 1-proteinase inhibitor may be abrogated by oxidative inactivation due to a concomitant stimulation of mesangial cell respiratory burst or in zones of close contact among cells or matrix, which have been shown to exclude antiproteinases.