Please use this identifier to cite or link to this item:
Title: Cytosolic and mitochondrial ROS in staurosporine-induced retinal cell apoptosis
Authors: Gil, Joana 
Almeida, Sandra 
Oliveira, Catarina R. 
Rego, A. Cristina 
Keywords: Apoptosis; Antioxidants; Calcium; Caspase-3; Mitochondria; Reactive oxygen species; Retinal cells; Staurosporine; Free radicals
Issue Date: 2003
Citation: Free Radical Biology and Medicine. 35:11 (2003) 1500-1514
Abstract: In this study, we investigated the involvement of reactive oxygen species (ROS) and calcium in staurosporine (STS)-induced apoptosis in cultured retinal neurons, under conditions of maintained membrane integrity. The antioxidants idebenone (IDB), glutathione-ethylester (GSH/EE), trolox, and Mn(III)tetrakis (4-benzoic acid) porphyrin chloride (MnTBAP) significantly reduced STS-induced caspase-3-like activity and intracellular ROS generation. Endogenous sources of ROS production were investigated by testing the effect of the following inhibitors: 7-nitroindazole (7-NI), a specific inhibitor of the neuronal isoform of nitric oxide synthase (nNOS); arachidonyl trifluoromethyl ketone (AACOCF3), a phospholipase A2 (PLA2) inhibitor; allopurinol, a xanthine oxidase inhibitor; and the mitochondrial inhibitors rotenone and oligomycin. All these compounds decreased caspase-3-like activity and ROS generation, showing that both mitochondrial and cytosolic sources of ROS are implicated in this mechanism. STS induced a significant increase in intracellular calcium concentration ([Ca2+]i), which was partially prevented in the presence of IDB and GSH/EE, indicating its dependence on ROS generation. These two antioxidants and the inhibitors allopurinol and 7-NI also reduced the number of TdT-mediated dUTP nick-end labeling-positive cells. Thus, endogenous ROS generation and the rise in intracellular calcium are important inter-players in STS-triggered apoptosis. Furthermore, the antioxidants may help to prolong retinal cell survival upon apoptotic cell death.
DOI: 10.1016/j.freeradbiomed.2003.08.022
Rights: openAccess
Appears in Collections:FMUC Medicina - Artigos em Revistas Internacionais

Files in This Item:
File Description SizeFormat
filee631db6392ac4c68a1af41f6eab39b3e.pdf396.6 kBAdobe PDFView/Open
Show full item record


checked on Aug 2, 2022

Page view(s) 20

checked on Aug 9, 2022

Download(s) 20

checked on Aug 9, 2022

Google ScholarTM




Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.