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Inhibition of cytoplasmic p53 differentially modulates Ca(2+) signaling and cellular viability in young and aged striata.
- Source :
-
Experimental gerontology [Exp Gerontol] 2014 Oct; Vol. 58, pp. 120-7. Date of Electronic Publication: 2014 Jul 30. - Publication Year :
- 2014
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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 Ca(2+) signaling and mitochondrial respiration, contributes to the loss of viability and ultimately leads to cell death. However, the link between Ca(2+) 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 μ) in the striatum of young and aged rats by evaluating Ca(2+) signaling, mitochondrial respiration, apoptotic protein expression, and tissue viability. Our results showed that pifithrin μ differentially modulated cytoplasmic and mitochondrial Ca(2+) 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 μ improved cell viability in aged tissue, reduced reactive oxygen species (ROS) generation, and reduced mitochondrial membrane potential (ΔΨm). Taken together, these results indicate that cytoplasmic p53 may have a special role in cell viability by influencing cellular Ca(2+) homeostasis and respiration and may produce differential effects in the striatum of young and aged rats.<br /> (Copyright © 2014 Elsevier Inc. All rights reserved.)
- Subjects :
- Age Factors
Aging pathology
Animals
Basal Ganglia metabolism
Basal Ganglia pathology
Basal Ganglia radiation effects
Calcium Signaling radiation effects
Cell Survival radiation effects
Glutamic Acid toxicity
Glutathione metabolism
Homeostasis
In Vitro Techniques
Membrane Potential, Mitochondrial drug effects
Mitochondria metabolism
Mitochondria radiation effects
Oxidative Stress drug effects
Phosphorylation
Rats, Wistar
Reactive Oxygen Species metabolism
Tumor Suppressor Protein p53 metabolism
Ultraviolet Rays
bcl-2-Associated X Protein metabolism
Aging metabolism
Basal Ganglia drug effects
Calcium Signaling drug effects
Cell Survival drug effects
Cytoplasm metabolism
Mitochondria drug effects
Sulfonamides pharmacology
Tumor Suppressor Protein p53 antagonists & inhibitors
Subjects
Details
- Language :
- English
- ISSN :
- 1873-6815
- Volume :
- 58
- Database :
- MEDLINE
- Journal :
- Experimental gerontology
- Publication Type :
- Academic Journal
- Accession number :
- 25084214
- Full Text :
- https://doi.org/10.1016/j.exger.2014.07.014