4-Hydroxy-3,5,3',4'-Tetrachlorobiphenyl Induced Membrane Permeability Transition in Isolated Rat Liver Mitochondria

Abstract

Summary Although much information about the apoptotic and other detrimental actions of polychlorinated biphenyls (PCBs) has been accumulated, the critical role of mitochondrial damage in such toxic action remains to be clarified. We have previously shown that PCBs affect various functions in isolated mitochondria. Recent studies have revealed that mitochondria play an important role in apoptosis through membrane permeability transition (MPT), and that Ca 2+ induces classic MPT characterized by depolarization and swelling of the mitochondria, thereby releasing cytochrome c in a cyclosporin A-sensitive mechanism [Free Rad. Res. 38, 29-35, 2004]. In the present study we investigated the effect of 4-hydroxy-3,5,3',4'-tetrachlorobiphenyl (4-OH-TCB) on isolated rat liver mitochondria in order to help clarify the effect of PCBs on MPT. Biochemical analysis revealed that 4-OH-TCB induced calcium release, reactive oxygen species (ROS) generation, depolarization, swelling and cytochrome c release in isolated rat liver mitochondria in a time and concentration dependent manner. These 4-OH-TCB-induced changes in mitochondrial function were found to be inhibited by the presence of cyclosporin A, suggesting an classic type of MPT. It is concluded that 4-OH-TCB induces MPT together with ROS generation, causing apoptosis in certain cells.

Effects of Endocrine Disrupting Chemicals on Amphibian Metamorphosis and Mitochondrial Membrane Permeability Transition

“…52,53,58) These findings indicate that CsA might affect not only pore opening of ANT by binding to cyclophilin D, but also affect the initial steps of MPT, including Ca 2+ transport. 52,59) In our investigation, 54) we observed that 4-OH-TCB disrupts mitochondrial functions as follows: in the presence of Pi and succinate, state 4 respiration increased with increasing concentration of 4-OH-TCB, while the respiratory control and oxidative phosphorylation activity ratios decreased; CsA prevented the effect of 4-OH-TCB on respiration. These results indicate that 4-OH-TCB possibly generates ROS by modulating the electron transport chain in the inner membrane of the mitochondria.…”

“…c from mitochondria. We 54) investigated the effect of the PCB compound, 4-hydroxy-3,3 ,4 ,5-tetrachlorobiphenyl (4-OH-TCB) on isolated rat liver mitochondria to help clarify the effect of PCBs on MPT. We found that 4-OH-TCB enhanced the uncoupling oxidative phosphorylation, the generation of reactive oxygen species (ROS), Ca 2+ release, membrane depolarization, swelling and Cyt.…”

Disruption of Thyroid Hormone Function by Environmental Pollutants

“…61) Moreover, our preliminary experiments have shown that 4-hydroxy-3,5,3 ,4 -tetrachlorobiphenyl (4-OH-TCB) enhances T 3 -induced Rana rugosa (R. rugosa) tadpole tail apoptosis in a concentration dependent manner. Recently Fujita et al 62) and Kashiwagi et al 63) reported that 4-OH-TCB induces MPT together with reactive oxygen species (ROS) generation, causing apoptosis.…”