17beta-estradiol suppresses ROS-induced apoptosis of CHO cells through inhibition of lipid peroxidation-coupled membrane permeability transition.
Oxidative stress-induced apoptotic cell death has been implicated to play a critical role in the mechanism of corpus luteum regression and follicular atresia. Recent studies suggests that reactive oxygen species (ROS) might play important roles in the regulation of luteal function. The present work describes the inhibitory effect of 17beta-estradiol (E2) on ROS-induced mitochondrial membrane permeability transition (MPT) and apoptosis of Chinese hamster ovary (CHO) cells. ROS generated by Fe2+ and H2O2 induced mitochondrial lipid peroxidation, depolarization, activation of caspase-3 and DNA fragmentation in CHO cells by some E2-inhibitable mechanism. E2 suppressed the Fe2+/H2O2-induced lipid peroxidation and MPT of isolated mitochondria that was characterized by cyclosporin A-inhibitable swelling, depolarization and cytochrome c release. Furthermore, E2 scavenged the xanthine oxidase generated ROS. These results suggests that Fe2+/H2O2 induced MPT and apoptosis of CHO cells by a mechanism that could be suppressed by antioxidant properties of E2.
Miyaguchi
Chosei
C
Department of Cell Chemistry, Okayama University Graduate School of Medicine and Dentistry, Okayama 700-8558, Japan.
Muranaka
Shikibu
S
Kanno
Tomoko
T
Fujita
Hirofumi
H
Akiyama
Jitsuo
J
Yoshioka
Tamotsu
T
Yasuda
Tatsuji
T
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D019556:COS Cells; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002413:Cations, Divalent / Q000494:pharmacology; D006224:Cricetinae; D045304:Cytochromes c / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology*; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007501:Iron / Q000737:chemistry / Q000494:pharmacology; D015227:Lipid Peroxidation / Q000187:drug effects*; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism*; D010539:Permeability / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism*
D002413:Cations, Divalent; D017382:Reactive Oxygen Species; D004958:Estradiol; D045304:Cytochromes c; D006861:Hydrogen Peroxide; D007501:Iron; D053148:Caspase 3; D020169:Caspases