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Accelerated Mitochondrial Reactive Oxygen Species Formation Induces OnsẸt of the Mitochondrial Permeability Transition and Mitochondrial Swelling in Cultured Hepatocytes After TNFα Exposure

Published online by Cambridge University Press:  02 July 2020

Ting Qian
Affiliation:
Department of Cell and Developmental Biology, University of North Carolina at Chapel Hill
John J. Lemasters
Affiliation:
Department of Cell and Developmental Biology, University of North Carolina at Chapel Hill
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Abstract

INTRODUCTION: The mitochondrial permeability transition (MPT) is implicated in mediating TNFα-induced apoptosis in cultured hepatocytes. Opening of permeability transition (PT) pores in the mitochondrial inner membrane causes the MPT. After the MPT, mitochondria swell, the outer membrane bursts, and pro-apoptotic cytochrome c is released into the cytosol. in isolated mitochondria, ROS formation promotes onset of the MPT. However, how mitochondrial ROS formation regulates the MPT in intact cells in TNFα-induced apoptosis is unknown. AIM: The present study was designed to determine the role of mitochondrial ROS formation in TNFα-induced MPT and apoptosis in cultured rat hepatocytes.

METHODS: Hepatocytes expressing an IkB superrepressor were pretreated with 2 μM t-BuOOH 4 hours before TNFα exposure with and without CsA (2 μM, an inhibitor of the PT pore) and the antioxidants, desferal (0.5 mM) or diphenylphenylendiamine (DPPD, 10 μM). Cell viability was monitored by propidium iodide fluorometry.

Type
Apoptosis in Health and Disease: Techniques for Detection and Biological Importance (Organized by M. Watanabe)
Copyright
Copyright © Microscopy Society of America 2001

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References

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