Mitochondrial Protein Phosphatase 2A Regulates Cell Death Induced by Simulated Ischemia in Kidney NRK-52E Cells

Acute renal failure can occur after an ischemic injury and results in significant mortality. The stress-signaling pathways that are activated during renal ischemia are unknown. PP2A has emerged as an important regulator of cell death. To study the role of PP2A in ischemia-induced cell death, we used...

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Bibliographic Details
Published in:Cell cycle (Georgetown, Tex.) Tex.), 2007-10, Vol.6 (19), p.2377-2385
Main Authors: Tsao, Chun Chui, Nica, Alina Felicia, Kurinna, Svitlana M., Jiffar, Tilahun, Mumby, Marc, Ruvolo, Peter P.
Format: Article
Language:English
Subjects:
Animals
Apoptosis
Binding
Biology
Bioscience
Calcium
Cancer
Caspases - metabolism
Cell
Cell Line
Ceramides - adverse effects
Cycle
Ischemia - metabolism
Kidney Tubules - blood supply
Kidney Tubules - cytology
Kidney Tubules - metabolism
Landes
Organogenesis
Protein Kinase C-alpha - metabolism
Protein Phosphatase 2 - drug effects
Protein Phosphatase 2 - metabolism
Proteins
Rats
RNA, Small Interfering - metabolism
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Summary:Acute renal failure can occur after an ischemic injury and results in significant mortality. The stress-signaling pathways that are activated during renal ischemia are unknown. PP2A has emerged as an important regulator of cell death. To study the role of PP2A in ischemia-induced cell death, we used an in vitro model of simulated ischemia. In the present study, simulated ischemia in rat renal tubule epithelial NRK-52E cells (a) results in cell death that involves both necrosis and apoptosis, (b) activates PP2A, and (c) up-regulates the PP2A B56 α regulatory subunit. Previous data have shown that PKC α negatively regulates B56 α protein expression. Consistent with this finding, simulated ischemia suppressed PKC α and up-regulated B56 α. Treatment of NRK-52E cells with ceramide suppressed PKC α and activated PP2A in a manner that mimicked simulated ischemia. A role for PP2A in simulated ischemia-induced cell death is likely since inhibition of PP2A protected NRK-52E cells. In addition, overexpression of exogenous B56 α but not B55 in NRK-52E cells enhanced simulated ischemia-induced cell death. These findings suggest that activation of a PP2A isoform that contains the B56 α regulatory subunit is required for ischemia-induced cell death in kidney epithelial proximal tubule cells.
ISSN:1538-4101
1551-4005
DOI:10.4161/cc.6.19.4737