Please use this identifier to cite or link to this item: https://doi.org/10.1016/S0891-5849(00)00421-4
Title: Superoxide radical-initiated apoptotic signalling pathway in selenite-treated HepG2 cells: Mitochondria serve as the main target
Authors: Shen, H.-M. 
Yang, C.-F.
Ding, W.-X.
Liu, J.
Ong, C.-N. 
Keywords: Apoptosis
Caspase
Cytochrome c
Free radicals
Mitochondria
Selenite
Superoxide radical
Issue Date: 1-Jan-2001
Citation: Shen, H.-M., Yang, C.-F., Ding, W.-X., Liu, J., Ong, C.-N. (2001-01-01). Superoxide radical-initiated apoptotic signalling pathway in selenite-treated HepG2 cells: Mitochondria serve as the main target. Free Radical Biology and Medicine 30 (1) : 9-21. ScholarBank@NUS Repository. https://doi.org/10.1016/S0891-5849(00)00421-4
Abstract: The exact role of superoxide radicals (O2 ·-) in apoptosis is still a matter of debate. The main objective of the present study is to evaluate the apoptotic signalling pathway initiated by O2 ·-. The reductive reaction of sodium selenite with glutathione was used as the intracellular O2 ·--generating system. When cells were exposed to 5 to 25 μM selenite, a temporal pattern of apoptotic events was observed following the elevation of O2 ·-, in which cytochrome c release and mitochondrial depolarization preceded caspase-3 activation and DNA fragmentation. The simultaneous treatment with N-acetylcysteine and 4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl markedly reduced O2 ·- level and suppressed the mitochondrial changes and the downstream apoptotic events. Moreover, pretreatment with cyclosporin A plus trifluoperazine, two mitochondrial permeability transition (MPT) inhibitors, was capable of attenuating O2 ·--mediated cytochrome c release and mitochondrial depolarization, and subsequently inhibiting apoptosis. Thus, the present results provide convincing evidence that O2 ·- generated from the reductive reaction of selenite with GSH is capable of triggering a mitochondria-dependent apoptotic pathway. Such knowledge may not only help to obtain a better understanding of the apoptotic effect of selenite per se, but of the role of O2 ·- in initiation and execution of apoptosis. © 2000 Elsevier Science Inc.
Source Title: Free Radical Biology and Medicine
URI: http://scholarbank.nus.edu.sg/handle/10635/113661
ISSN: 08915849
DOI: 10.1016/S0891-5849(00)00421-4
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