Please use this identifier to cite or link to this item:
https://hdl.handle.net/10316/5792
DC Field | Value | Language |
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dc.contributor.author | Custódio, José B. A. | - |
dc.contributor.author | Cardoso, Carla M. P. | - |
dc.contributor.author | Almeida, Leonor M. | - |
dc.date.accessioned | 2008-09-26T17:41:50Z | - |
dc.date.available | 2008-09-26T17:41:50Z | - |
dc.date.issued | 2002 | en_US |
dc.identifier.citation | Chemico-Biological Interactions. 140:2 (2002) 169-184 | en_US |
dc.identifier.uri | https://hdl.handle.net/10316/5792 | - |
dc.description.abstract | Etoposide (VP-16) is known to promote cell apoptosis either in cancer or in normal cells as a side effect. This fact is preceded by the induction of several mitochondrial events, including increase in Bax/Bcl-2 ratio followed by cytochrome c release and consequent activation of caspase-9 and -3, reduction of ATP levels, depolarization of membrane potential ([Delta][Psi]) and rupture of the outer membrane. These events are apoptotic factors essentially associated with the induction of the mitochondrial permeability transition (MPT). VP-16 has been shown to stimulate the Ca2+-dependent MPT induction similarly to prooxidants and to promote apoptosis by oxidative stress mechanisms, which is prevented by glutathione (GSH) and N-acetylcysteine (NAC). Therefore, the aim of this work was to study the effects of antioxidants and thiol protecting agents on MPT promoted by VP-16, attempting to identify the underlying mechanisms on VP-16-induced apoptosis. The increased sensitivity of isolated mitochondria to Ca2+-induced swelling, Ca2+ release, depolarization of [Delta][Psi] and uncoupling of respiration promoted by VP-16, which are prevented by cyclosporine A proving that VP-16 induces the MPT, are also efficiently prevented by ascorbate, the primary reductant of the phenoxyl radicals produced by VP-16. The thiol reagents GSH, dithiothreitol and N-ethylmaleimide, which have been reported to prevent the MPT induction, also protect this event promoted by VP-16. The inhibition of the VP-16-induced MPT by antioxidants agrees with the prevention of etoposide-induced apoptosis by GSH and NAC and suggests the generation of oxidant species as a potential mechanism underlying the MPT that may trigger the release of mitochondrial apoptogenic factors responsible for apoptotic cascade activation. | en_US |
dc.description.uri | http://www.sciencedirect.com/science/article/B6T56-45MDTK0-1/1/8c058bbb86c4e2aa262e5705ce08671f | en_US |
dc.format.mimetype | aplication/PDF | en |
dc.language.iso | eng | eng |
dc.rights | openAccess | eng |
dc.subject | Etoposide | en_US |
dc.subject | Anticancer | en_US |
dc.subject | Apoptosis | en_US |
dc.subject | Mitochondrial permeability transition | en_US |
dc.subject | Antioxidants | en_US |
dc.subject | Oxidative stress | en_US |
dc.title | Thiol protecting agents and antioxidants inhibit the mitochondrial permeability transition promoted by etoposide: implications in the prevention of etoposide-induced apoptosis | en_US |
dc.type | article | en_US |
dc.identifier.doi | 10.1016/S0009-2797(02)00020-0 | - |
item.fulltext | Com Texto completo | - |
item.openairecristype | http://purl.org/coar/resource_type/c_18cf | - |
item.grantfulltext | open | - |
item.languageiso639-1 | en | - |
item.openairetype | article | - |
item.cerifentitytype | Publications | - |
crisitem.author.orcid | 0000-0002-7769-4712 | - |
Appears in Collections: | FFUC- Artigos em Revistas Internacionais |
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filed137a22fb1134e428fd025e426b86dae.pdf | 286.39 kB | Adobe PDF | View/Open |
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