TY - JOUR
T1 - Induction of the mitochondrial permeability transition by selenium compounds mediated by oxidation of the protein thiol groups and generation of the superoxide
AU - Kim, Tae Soo
AU - Yun, Byung Yup
AU - Kim, Ick Young
N1 - Funding Information:
We are grateful for the comments of the anoymous reviewers. This work is supported in part by National Natural Science Funds of China(No.61272221, 61170181) and Jiangsu University Philosophy and Social Science Fund(No.2016SJB740004).
Funding Information:
We are grateful for the comments of the anoymous reviewers. This work is sup ported in part by National Natural Science Funds of China(No.61272221, 61170181) and Jiangsu University Philosophy and Social Science Fund(No.2016SJB740004).
PY - 2003/12/15
Y1 - 2003/12/15
N2 - The cancer chemopreventive effect of selenium compounds cannot be fully explained by the role of selenium as a component of antioxidant enzymes, suggesting that other mechanisms, such as thiol oxidation or free radical generation, also underlie this effect. The toxicities of six different selenium compounds (selenite, selenate, selenocystine, selenocystamine, selenodioxide, and selenomethionine) have now been compared in HepG2 human hepatoma cells and isolated rat liver mitochondria. Selenite, selenocystine, and selenodioxide induced apoptosis in HepG2 cells and mediated oxidation of protein thiol groups in both HepG2 cells and isolated mitochondria. Selenocystamine oxidized protein thiol groups in isolated mitochondria and crude extracts of HepG2 cells but not in intact HepG2 cells, suggesting that this compound is not able to cross the cell membrane. The selenium compounds capable of oxidizing thiol groups also induced the mitochondrial permeability transition (MPT) in isolated mitochondria. Furthermore, they generated the superoxide (O2·-) on reaction with glutathione in the presence of mitochondria, and an O2·- scavenger inhibited their induction of the MPT. These results suggest that the pro-apoptotic action of selenium compounds is mediated by both thiol oxidation and the generation of O2·-, both of which contribute to opening of the MPT pore.
AB - The cancer chemopreventive effect of selenium compounds cannot be fully explained by the role of selenium as a component of antioxidant enzymes, suggesting that other mechanisms, such as thiol oxidation or free radical generation, also underlie this effect. The toxicities of six different selenium compounds (selenite, selenate, selenocystine, selenocystamine, selenodioxide, and selenomethionine) have now been compared in HepG2 human hepatoma cells and isolated rat liver mitochondria. Selenite, selenocystine, and selenodioxide induced apoptosis in HepG2 cells and mediated oxidation of protein thiol groups in both HepG2 cells and isolated mitochondria. Selenocystamine oxidized protein thiol groups in isolated mitochondria and crude extracts of HepG2 cells but not in intact HepG2 cells, suggesting that this compound is not able to cross the cell membrane. The selenium compounds capable of oxidizing thiol groups also induced the mitochondrial permeability transition (MPT) in isolated mitochondria. Furthermore, they generated the superoxide (O2·-) on reaction with glutathione in the presence of mitochondria, and an O2·- scavenger inhibited their induction of the MPT. These results suggest that the pro-apoptotic action of selenium compounds is mediated by both thiol oxidation and the generation of O2·-, both of which contribute to opening of the MPT pore.
KW - Apoptosis
KW - Mitochondria
KW - Mitochondria permeability transition
KW - Selenium compounds
KW - Superoxide anion
UR - http://www.scopus.com/inward/record.url?scp=0344944226&partnerID=8YFLogxK
U2 - 10.1016/j.bcp.2003.08.021
DO - 10.1016/j.bcp.2003.08.021
M3 - Article
C2 - 14637188
AN - SCOPUS:0344944226
VL - 66
SP - 2301
EP - 2311
JO - Biochemical Pharmacology
JF - Biochemical Pharmacology
SN - 0006-2952
IS - 12
ER -