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Title: Aspirin-induced apoptosis of yeast cells is associated with mitochondrial superoxide radical accumulation and NAD(P)H oxidation
Authors: Farrugia, Gianluca
Bannister, William H.
Vassallo, Neville
Balzan, Rena
Keywords: Aspirin -- Therapeutic use
Superoxide dismutase
Pyridine nucleotides
Issue Date: 2013
Publisher: John Wiley & Sons Ltd.
Citation: Farrugia, G., Bannister, W. H., Vassallo, N., & Balzan, R. (2013). Aspirin-induced apoptosis of yeast cells is associated with mitochondrial superoxide radical accumulation and NAD (P) H oxidation. FEMS Yeast Research, 13(8), 755-768.
Abstract: In previous studies, we observed that aspirin, a promising cancer-preventive agent, induces apoptosis in mitochondrial manganese superoxide dismutase(MnSOD)-deficient Saccharomyces cerevisiae cells grown aerobically in ethanol medium. In this study, we show that aspirin-induced apoptosis is associated with a significant increase in mitochondrial and cytosolic O2 and oxidation of mitochondrial NAD(P)H. A concomitant rise in the level of cytosolic CuZn-SOD activity failed to compensate for mitochondrial MnSOD deficiency. However, an observed increase in activity of Escherichia coli FeSOD targeted to the mitochondrial matrix of the MnSOD-deficient yeast cells, markedly decreased aspirin-induced accumulation of mitochondrial O 2 , significantly increased the mitochondrial NAD(P)H level and rescued the apoptotic phenotype. Indeed, recombinant yeast cells expressing E. coli FeSOD behaved in a similar manner to the parent wild-type yeast cells with native mitochondrial MnSOD activity. Wild-type cells consistently showed a decrease in mitochondrial O 2 and an increase in mitochondrial NAD(P)H levels in the presence of aspirin in ethanol medium. In fact, in wild-type cells, our studies supported an antioxidant action of aspirin. Taken together, our results indicate that a pro-oxidant effect of aspirin occurring predominantly in cells with compromised mitochondrial redox balance may be enough to overcome antioxidant defences resulting in apoptosis, as observed in MnSOD-deficient yeast cells.
Appears in Collections:Scholarly Works - FacM&SPB

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