Bcl-2 protects against apoptosis induced by antimycin A and bongkrekic acid without restoring cellular ATP levels

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• 作者：de Graaf ; Aniek O. ; Meijerink ; Jules P.P. ; van den Heuvel ; Lambert P. ; DeAbreu ; Ronney A. ; et. al.
• 关键词：Bcl-2 ; ATP ; Mitochondrion ; Apoptosis ; Adenine nucleotide translocator ; Voltage-dependent anion channel ; AA ; antimycin A ; AIF ; apoptosis inducing factor ; ANT ; adenine nucleotide translocator ; BA ; bongkrekic acid ; DMEM ; Dulbecco's modified Eagle medium ; GF
• 刊名：Biochimica et Biophysica Acta (BBA)/Bioenergetics
• 出版年：2002
• 出版时间：April 22, 2002
• 年：2002
• 卷：1554
• 期：1-2
• 页码：57-65
• 全文大小：309 K

文摘

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.