Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 167-175 |
| Number of pages | 9 |
| Journal | Journal of Clinical Biochemistry and Nutrition |
| Volume | 38 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - May 2006 |
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Keywords
- Apoptosis
- Membrane permeability transition
- Mitochondria
- Polychlorinated biphenyls
- Reactive oxygen species
ASJC Scopus subject areas
- Medicine (miscellaneous)
- Food Science
Cite this
4-Hydroxy-3,5,3′,4′-tetrachlorobiphenyl induced membrane permeability transition in isolated rat liver mitochondria. / Fujita, Hirofumi; Okimura, Yuya; Utsumi, Toshihiko; Kitamura, Shigeyuki; Kuroki, Hiroaki; Otsuki, Takemi; Sasaki, Junzo; Kashiwagi, Akihiko; Utsumi, Kozo.
In: Journal of Clinical Biochemistry and Nutrition, Vol. 38, No. 3, 05.2006, p. 167-175.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - 4-Hydroxy-3,5,3′,4′-tetrachlorobiphenyl induced membrane permeability transition in isolated rat liver mitochondria
AU - Fujita, Hirofumi
AU - Okimura, Yuya
AU - Utsumi, Toshihiko
AU - Kitamura, Shigeyuki
AU - Kuroki, Hiroaki
AU - Otsuki, Takemi
AU - Sasaki, Junzo
AU - Kashiwagi, Akihiko
AU - Utsumi, Kozo
PY - 2006/5
Y1 - 2006/5
N2 - 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.
AB - 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.
KW - Apoptosis
KW - Membrane permeability transition
KW - Mitochondria
KW - Polychlorinated biphenyls
KW - Reactive oxygen species
UR - http://www.scopus.com/inward/record.url?scp=33646820093&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33646820093&partnerID=8YFLogxK
U2 - 10.3164/jcbn.38.167
DO - 10.3164/jcbn.38.167
M3 - Article
VL - 38
SP - 167
EP - 175
JO - Journal of Clinical Biochemistry and Nutrition
JF - Journal of Clinical Biochemistry and Nutrition
SN - 0912-0009
IS - 3
ER -