Bcl-2 protects against apoptosis induced by antimycin A and bongkrekic acid without restoring cellular ATP levels.
SourceBiochimica et Biophysica Acta. Bioenergetics, 1554, 1-2, (2002), pp. 57-65
Article / Letter to editor
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Paediatrics - OUD tm 2017
Biochimica et Biophysica Acta. Bioenergetics
SubjectInborn errors of metabolism; Pediatric Oncology. Treatment of children with cancer.; Disturbances in biochemical and functional development of the kidney during childhood.; CHL; Erfelijke stofwisselingsziekten; Haematology; Kinderoncologie. Behandeling van kinderen met kanker.; Stoornissen in de biochemische en functionele ontwikkeling van de nier op kinderleeftijd
Several studies indicate that mitochondrial ATP production as well as ADP/ATP exchange across mitochondrial membranes are impaired during apoptosis. We investigated whether Bcl-2 could protect against cell death under conditions in which ATP metabolism is inhibited. Inhibition of ATP production using antimycin A (AA) (complex III inhibition) combined with inhibition of ADP/ATP exchange by bongkrekic acid (BA) (adenine nucleotide translocator (ANT) inhibition) induced a sharp decrease in total cellular ATP in FL5.12 parental cells (to 35% of untreated controls after 24 h of incubation). Within 24 and 48 h, 38% and 75% of the cells had died, respectively. However, in stably transfected FL5.12 Bcl-2 subclones, no cell death occurred under these experimental conditions. Similar results were obtained with Jurkat and Bcl-2 overexpressing Jurkat cells. Total cellular ATP levels were equally affected in FL5.12 Bcl-2 overexpressing cells and FL5.12 parental cells. This indicates that Bcl-2 overexpressing cells are able to survive with very low cellular ATP content. Furthermore, Bcl-2 did not protect against cell death by restoring ATP levels. This suggests that, under these conditions, Bcl-2 acts by inhibiting the signalling cascade triggered by the inhibitors that would normally lead to apoptosis.
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