Aspirin-induced apoptosis of yeast cells is associated with mitochondrial superoxide radical accumulation and NAD(P)H oxidation

Farrugia, Gianluca; Bannister, W.H.; Vassallo, Neville; Balzan, Rena

doi:10.1111/1567-1364.12075

Cited by 11 publications

(8 citation statements)

References 47 publications

(83 reference statements)

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“…Slightly elevated adduct rates in WBC were determined in few welders using acetylsalicylic acid as medication. The latter observation is in line with in vitro studies where acetylsalicylic acid induced apoptosis by increasing the production of ROS (Farrugia et al 2013 ; Raza et al 2011 ).…”

Section: Discussionsupporting

confidence: 84%

Oxidatively damaged guanosine in white blood cells and in urine of welders: associations with exposure to welding fumes and body iron stores

et al. 2014

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The International Agency for Research on Cancer considers the carcinogenicity of welding fume of priority for re-evaluation. Genotoxic effects in experimental animals are still inconclusive. Here, we investigated the association of personal exposure to metals in respirable welding fumes during a working shift with oxidatively damaged guanosine in DNA of white blood cells (WBC) and in postshift urine samples from 238 welders. Medians of 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodGuo) were 2.35/106 dGuo in DNA of WBC and 4.33 µg/g creatinine in urine. The median of 8-oxo-7,8-dihydroguanosine (8-oxoGuo) was 7.03 µg/g creatinine in urine. The extent of both urinary parameters was higher in welders applying techniques with high particle emission rates to stainless steel than in tungsten inert gas welders (8-oxodGuo: 9.96 vs. 4.49 µg/L, 8-oxoGuo: 15.7 vs. 7.7 µg/L), but this apparent difference diminished after creatinine adjustment. We applied random intercept models to estimate the influence of airborne and systemic exposure to metals on oxidatively damaged guanosine in WBC and urine together with covariates. We observed a highly significant nonlinear association of urinary 8-oxoGuo with serum ferritin (P < 0.0001) and higher 8-oxoGuo concentrations for respirable iron >1,000 µg/m3 compared to ≤57 µg/m3. Similar effects were found for manganese. Airborne chromium but not nickel was associated with all oxidatively modified guanosine measures, whereas urinary chromium as well as nickel showed associations with urinary modified guanosines. In summary, oxidatively damaged urinary guanosine was associated with airborne and systemic exposure to metals in welders and showed a strong relation to body iron stores.Electronic supplementary materialThe online version of this article (doi:10.1007/s00204-014-1319-2) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 84%

Oxidatively damaged guanosine in white blood cells and in urine of welders: associations with exposure to welding fumes and body iron stores

et al. 2014

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“…and oxidation of mitochondrial nicotinamide adenine dinucleotide phosphate hydrogen. 8 However, the mechanism underlying the effect of aspirin is still unclear.…”

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confidence: 99%

Aspirin Causes Lipid Accumulation and Damage to Cell Membrane by Regulating DCI1/OLE1 in Saccharomyces cerevisiae

Zhu

Yan

et al. 2020

Microbial Drug Resistance

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Aspirin is one of the most commonly used nonsteroidal anti-inflammatory drugs. Various potential pharmacological effects of aspirin, such as anticancer, antibacterial activity, and prolonging life expectancy have been discovered. However, the mechanism of aspirin is not fully elucidated. Herein, the effects of aspirin on fatty acid metabolism in yeast cell model Saccharomyces cerevisiae were studied. The results showed that aspirin can induce lipid accumulation and reduce the unsaturated fat index in cells. The assessment of cell membrane integrity demonstrated that aspirin caused damage to the cell membrane. These effects of aspirin were attributed to the alterations of the expression of DCI1 and OLE1. Similarly, aspirin was able to cause lipid accumulation and damage to the cell membrane by interfering with the expression of OLE1 in Candida albicans. These findings are expected to improve current understanding of the mode of action of aspirin and provide a novel strategy for antifungal drug design.

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“…cerevisiae cells, but not in wild-type yeast cells, during aerobic growth in ethanol medium 18–21 . We also showed that the aspirin-induced apoptosis in redox-compromised MnSOD-deficient yeast cells is associated with severe mitochondrial dysfunction, including events such as overproduction of mitochondrial superoxide radicals (O 2 ˙ − ), oxidation of mitochondrial NAD(P)H 21 , decreased respiration, release of cytochrome c and disruption of the mitochondrial membrane potential 20 . Overall, these results indicated that the mitochondrial milieu constitutes a critical cellular target of aspirin.…”

Section: Introductionmentioning

confidence: 92%

Aspirin impairs acetyl-coenzyme A metabolism in redox-compromised yeast cells

Farrugia

Azzopardi

Saliba

et al. 2019

Sci Rep

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Aspirin is a widely used anti-inflammatory and antithrombotic drug also known in recent years for its promising chemopreventive antineoplastic properties, thought to be mediated in part by its ability to induce apoptotic cell death. However, the full range of mechanisms underlying aspirin’s cancer-preventive properties is still elusive. In this study, we observed that aspirin impaired both the synthesis and transport of acetyl-coenzyme A (acetyl-CoA) into the mitochondria of manganese superoxide dismutase (MnSOD)-deficient Saccharomyces cerevisiae EG110 yeast cells, but not of the wild-type cells, grown aerobically in ethanol medium. This occurred at both the gene level, as indicated by microarray and qRT-PCR analyses, and at the protein level as indicated by enzyme assays. These results show that in redox-compromised MnSOD-deficient yeast cells, but not in wild-type cells, aspirin starves the mitochondria of acetyl-CoA and likely causes energy failure linked to mitochondrial damage, resulting in cell death. Since acetyl-CoA is one of the least-studied targets of aspirin in terms of the latter’s propensity to prevent cancer, this work may provide further mechanistic insight into aspirin’s chemopreventive behavior with respect to early stage cancer cells, which tend to have downregulated MnSOD and are also redox-compromised.

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Aspirin-induced apoptosis of yeast cells is associated with mitochondrial superoxide radical accumulation and NAD(P)H oxidation

Cited by 11 publications

References 47 publications

Oxidatively damaged guanosine in white blood cells and in urine of welders: associations with exposure to welding fumes and body iron stores

Oxidatively damaged guanosine in white blood cells and in urine of welders: associations with exposure to welding fumes and body iron stores

Aspirin Causes Lipid Accumulation and Damage to Cell Membrane by Regulating DCI1/OLE1 in Saccharomyces cerevisiae

Aspirin impairs acetyl-coenzyme A metabolism in redox-compromised yeast cells

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