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The Ca2+ signal as common target of three different proteins involved in the apoptotic process.

Marchi, Saverio (2010) The Ca2+ signal as common target of three different proteins involved in the apoptotic process. PhD Thesis , Università degli Studi di Ferrara.

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    Ca2+ signal plays a fundamental role in modulating a diverse range of cellular responses including muscle contraction, exocytosis, motility, fertilization, proliferation and apoptosis. Therefore, several proteins involved in this wide range of biological processes “manipulate” intracellular Ca2+ to (dis)regulate these events. To analyse Ca2+ homeostasis at the subcellular level, we employed the Ca2+-sensitive photoprotein aequorin, targeted to defined intracellular locations (organelles, such as mitochondria, endoplasmic reticulum, and cytoplasmic regions). Using this experimental approach, we investigated multiple effects on Ca2+ dynamics of three different proteins: i) the role of 66 KDa isoform of Shc (p66Shc) on the alterations of mitochondrial Ca2+ homeostasis observed after oxidative stress, and elucidation of specific signalling route leading to its mitochondrial import. ii) The tumor suppressor protein Fhit sensitizes the low-affinity Ca2+ transporters of mitochondria, enhancing Ca2+ uptake into the organelle both in intact and in permabilized cells, and potentiating the effect of apoptotic agents. iii) The proto-oncogene Akt, a potent inhibitor of apoptosis, reduces Ca2+ release from the ER induced either by agonist stimulation or by apoptotic stimuli and this alteration of ER Ca2+ content and release, reduces significantly cellular sensitivity to Ca2+ mediated proapoptotic stimulation. Taken together these data remark the practical useful of Ca2+-dynamics investigation as a “reporter system” to understand different molecular mechanisms of different proteins and may provide ways to act on various biological processes, especially on apoptotic cell death and its derangement in cancer.

    Item Type:Thesis (PhD Thesis)
    Date:19 March 2010
    Tutor:Rimessi, Alessandro
    Coordinator:Borea, Andrea
    Institution:Università degli Studi di Ferrara
    Divisions:Dipartimento > Medicina clinica e sperimentale
    Subjects:Area 06 - Scienze mediche > MED/04 Patologia generale
    Uncontrolled Keywords:calcio, apoptosi, p66Shc, Akt, Fhit, equorina, calcium, apoptosis, aequorin
    Deposited on:23 Jul 2010 09:55


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