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Title: Inhibition of cytoplasmic p53 differentially modulates Ca2+ signaling and cellular viability in young and aged striata
Authors: Ureshino, Rodrigo Portes [UNIFESP]
Hsu, Yi-Te
Garcez-do-Carmo, Lucia [UNIFESP]
Yokomizo, Cesar Henrique
Nantes, Iseli Lourenco
Smaili, Soraya Soubhi [UNIFESP]
Universidade Federal de São Paulo (UNIFESP)
Med Univ S Carolina
Fed Univ ABC
Keywords: Aging
Oxygen consumption
Issue Date: 1-Oct-2014
Publisher: Elsevier B.V.
Citation: Experimental Gerontology. Oxford: Pergamon-Elsevier B.V., v. 58, p. 120-127, 2014.
Abstract: The p53 protein, a transcription factor with many gene targets, can also trigger apoptosis in the cytoplasm. the disruption of cell homeostasis, such as Ca2+ signaling and mitochondrial respiration, contributes to the loss of viability and ultimately leads to cell death. However, the link between Ca2+ signaling and p53 signaling remains unclear. During aging, there are alterations in cell physiology that are commonly associated with a reduced adaptive stress response, thus increasing cell vulnerability. in this work, we examined the effects of a cytoplasmic p53 inhibitor (pifithrin mu) in the striatum of young and aged rats by evaluating Ca2+ signaling, mitochondrial respiration, apoptotic protein expression, and tissue viability. Our results showed that pifithrin mu differentially modulated cytoplasmic and mitochondrial Ca2+ in young and aged rats. Cytoplasmic p53 inhibition appeared to reduce the mitochondrial respiration rate in both groups. in addition, p53 phosphorylation and Bax protein levels were elevated upon cytoplasmic p53 inhibition and could contribute to the reduction of tissue viability. Following glutamate challenge, pifithrin mu improved cell viability in aged tissue, reduced reactive oxygen species (ROS) generation, and reduced mitochondrial membrane potential (Delta Psi m). Taken together, these results indicate that cytoplasmic p53 may have a special role in cell viability by influencing cellular Ca2+ homeostasis and respiration and may produce differential effects in the striatum of young and aged rats. (C) 2014 Elsevier Inc. All rights reserved.
ISSN: 0531-5565
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Appears in Collections:Em verificação - Geral

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