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

Chun Chui Tsao, Alina Felicia Nica, Svitlana M. Kurinna, Tilahun Jiffar, Marc Mumby and Peter P. Ruvolo

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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.

Authors

Chun Chui Tsao

University of Texas Health Science Center; Houston, Texas

Alina Felicia Nica

University of Texas Health Science Center; Houston, Texas

Svitlana M. Kurinna

University of Texas Health Science Center; Houston, Texas

Tilahun Jiffar

University of Texas Health Science Center; Houston, Texas

Marc Mumby

University of Texas Southwestern Medical Center; Dallas, TX

Peter P. Ruvolo

The University of Texas Health Science Center; Houston, Texas

Purchase article for $19

Subscribe to this journal for $129/year