1,721,553 research outputs found

    Pivotal role of superoxides generated in the mitochondrial respiratory chain in peroxynitrite-dependent activation of phospholipase A2.

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    Exposure of PC12 cells to reagent peroxynitrite promotes the release of arachidonic acid (AA) mediated by activation of phospholipase A(2) [Guidarelli, Palomba and Cantoni (2000) Br. J. Pharmacol. 129, 1539-1542]. We now present experimental evidence consistent with the notion that this response is not directly triggered by peroxynitrite but, rather, by reactive oxygen species generated at the level of complex III of the mitochondrial respiratory chain, In particular, superoxide (and not hydrogen peroxide) has a pivotal role in peroxynitrite-dependent activation of phospholipase A(2). This observation was confirmed by results showing that superoxide, or peroxynitrite, promotes release of AA in isolated mitochondria. Consistently, the release of AA elicited by either peroxynitrite or A23187 in intact cells was shown to be calcium-dependent and differentially affected by phospholipase A, inhibitors with different levels of specificity. In particular, the effects of peroxynitrite, unlike those of A23187, were both sensitive to low concentrations of two general phospholipase A, inhibitors and insensitive to arachidonyltrifluoromethyl ketone, which shows some selectivity towards cytosolic phospholipase A(2). In addition, peroxynitrite and A23187 synergistically enhanced the release of AA. Collectively, the above results demonstrate that peroxynitrite causes inhibition of complex III, followed by enforced formation of superoxides that stimulate the activity of a calcium-dependent PLA, isoform, probably localized in the mitochondria

    Peroxynitrite damages U937 cell DNA via the intermediate formation of mitochondrial oxidants.

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    Eight years ago we published in this journal the first evidence that peroxynitrite does not directly produce DNA single-strand breakage in intact U937 cells (Guidarelli et al., IUBMB Life 50. 195-201). This event was rather attributed to the secondary reactive species produced at the mitochondrial level via a Ca2+-dependent reaction in which ubisemiquinone serves as an electron donor. Under these conditions, electrons are directly transferred to molecular oxygen and superoxide/H2O2, and the ensuing DNA damage can therefore be produced in a time dependent manner for at least 30 min. Formation of H2O2 and DNA single-strand breaks was therefore dependent on interference with electron transport at the complex Ill level as well as on mitochondrial Ca2+ accumulation. Further studies led to the demonstrations that peroxynitrite mobilizes Ca2+ from the ryanodine receptor. Finally. in U937 cells, a pro-monocytic cell line sharing with monocytes/macrophages the same signaling events to survive to peroxynitrite. mitochondrial H2O2 promotes inhibition of survival via tyrosine phosphatase activation, leading to ERK1/2 dephosphorylation and thus to upstream inhibition of the survival signaling

    Venetia riflessa sull'acqua: ipotesi e nuove ricerche

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    The essay aims to investigate for the first time in a systematic way the plan of Venice (Venetia) by Gian Battista Arzenti, a canvas painted in oil, collected at the Correr Museum and recently dated to 1621-26 (by Gianmario Guidarelli 2015). The plan depicts the city as a very compact and homogeneous body, at a time in its urban history when part of the great transformations designed by Cristoforo Sabbadino in the previous century have now come to an end. The painter's gaze offers an almost isotropic view of the city, where the Marciana area (which has a central role in previous depictions, such as that of Jacopo de 'Barbari, 1500) is only one of the celebratory fulcrums of the city, together with the Grand Canal (with its parade of patrician palaces) and the Arsenate. In this visual reworking of Venice, the rote of monasteries and convents is central, but not predominant compared to the other elements of the city. The marble facades of the Benedictine churches of San Zaccaria and San ..

    I Predicatori dei Santi Giovanni e Paolo e Venezia: strategie di insediamento e dinamiche urbane

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    The urban development of Venice, especially in the XIII and XIV centuries, was strongly influenced by the presence of the settlements of the Mendicant Orders. In particular, in the marginal areas of the city, the construction of churches and convents, often of large dimensions, influenced the growth of the city the definition of its shape and the economic and social transformations. The case of the convent of the friar. Preacher Santi Giovanni e Paolo i particularly useful for investigating these dynamics because the northern side of the city was already on the way toward a process of proto-industrialization in the XIII century. Yet, the same analysis can be carried out by expanding to a more systematic approach, also considering the dynamics of residential settlement, which in an area that has always been characterized by a considerable social variety can be used as sort of litmus papers to precisely and clearly identify the real impact of the foundation of a Dominican convent on a rapidly changing city. The proposed analysis also makes use of digital technologies and considers transformations up to the XVIII century, when the island doubled in size and took on new urban functions, precisely because of the presence of the convent
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