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Title: | L-glutamate delays aspirin-induced apoptosis of redox-compromised yeast cells by restoring the GSH/GSSG ratio and the mitochondrial respiratory rate |
Other Titles: | 10th Malta Medical School Conference : conference abstract book |
Authors: | Azzopardi, Maria Farrugia, Gianluca Saliba, Christian Gross, Angelina S. Vassallo, Neville Grech, Godfrey Borg, Joseph J. Madeo, Frank Eisenberg, Tobias Balzan, Rena |
Keywords: | Nonsteroidal anti-inflammatory agents Aspirin Apoptosis Cancer cells Superoxide dismutase Saccharomyces cerevisiae Cell cycle Glutamic acid |
Issue Date: | 2018 |
Publisher: | University of Malta. Medical School |
Citation: | Azzopardi, M., Farrugia, G., Saliba, C., Gross, A.E., Vassallo, N., Grech, G…. Balzan, R. (2018). L-glutamate delays aspirin-induced apoptosis of redox-compromised yeast cells by restoring the GSH/GSSG ratio and the mitochondrial respiratory rate. In P. Schembri-Wismayer, R. Galea, C. Scerri, R. Muscat & A. Fenech (Eds.), 10th Malta Medical School Conference : conference abstract book (pp. 44). |
Abstract: | Introduction: We showed that aspirin induces apoptosis in Saccharomyces cerevisiae EG110 cells deficient in manganese superoxide dismutase (MnSOD) cultivated in ethanol medium, but not in wild-type EG103 cells. Our microarray study revealed an aspirin-induced downregulation of SNO1 and SNZ1 in the mutant strain. Together, these genes encode a glutamine amidotransferase complex that produces glutamate: a key metabolite involved in synthesising the antioxidant glutathione (GSH) and the tricarboxylic acid (TCA) cycle intermediate, α-ketoglutarate. Methods: Upon confirmation of gene expression by RT-qPCR, the growth of aspirin-treated EG110 cells supplemented with L-glutamate was monitored via optical density measurements (OD600). The effect of glutamate was confirmed by viability studies, based on colony forming units (CFUs) and flow-cytometric analysis. Further experiments involved the measurement of intracellular GSH and GSSG levels, as well as respirometry measurements. Results: We observed that aspirin-induced apoptosis of EG110 cells is significantly delayed by the addition of 200mM L-glutamate. Furthermore, we show that this rescuing effect is due to a restored GSH/GSSG ratio, as well as a restored mitochondrial respiratory rate. Conclusion: The influence of aspirin on glutamate metabolism in our redox-compromised cells, suggests that their death is preceded by redox imbalance, as shown by a lowered GSH/GSSG ratio and oxidative stress accompanied by decreased respiratory rate. Rescuing by exogenous glutamate is likely mediated by increased synthesis of cellular GSH and the anaplerotic supply of α -ketoglutarate to the TCA cycle. This aspirin-induced effect on glutamate metabolism may help us better understand the antineoplastic effect of aspirin on early-stage cancer cells which are also redox-compromised. Disclosures: Project “R&I-2015-001” is being financed by the Malta Council for Science and Technology through the R&I Technology Development Programme. |
URI: | https://www.um.edu.mt/library/oar/handle/123456789/99680 |
ISSN: | 18133339 |
Appears in Collections: | Scholarly Works - FacHScABS |
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