scholarly journals Hydrogen peroxide induced loss of heterozygosity correlates with replicative lifespan and mitotic asymmetry inSaccharomyces cerevisiae

PeerJ ◽  
2016 ◽  
Vol 4 ◽  
pp. e2671 ◽  
Author(s):  
Emine Güven ◽  
Lindsay A. Parnell ◽  
Erin D. Jackson ◽  
Meighan C. Parker ◽  
Nilin Gupta ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Hydrogen Peroxide ◽  
Genomic Instability ◽  
Loss Of Heterozygosity ◽  
Population Level ◽  
Cellular Aging ◽  
Yeast Cells ◽  
Replicative Lifespan ◽  
Chronological Aging ◽  
Transition Points

Cellular aging inSaccharomyces cerevisiaecan lead to genomic instability and impaired mitotic asymmetry. To investigate the role of oxidative stress in cellular aging, we examined the effect of exogenous hydrogen peroxide on genomic instability and mitotic asymmetry in a collection of yeast strains with diverse backgrounds. We treated yeast cells with hydrogen peroxide and monitored the changes of viability and the frequencies of loss of heterozygosity (LOH) in response to hydrogen peroxide doses. The mid-transition points of viability and LOH were quantified using sigmoid mathematical functions. We found that the increase of hydrogen peroxide dependent genomic instability often occurs before a drop in viability. We previously observed that elevation of genomic instability generally lags behind the drop in viability during chronological aging. Hence, onset of genomic instability induced by exogenous hydrogen peroxide treatment is opposite to that induced by endogenous oxidative stress during chronological aging, with regards to the midpoint of viability. This contrast argues that the effect of endogenous oxidative stress on genome integrity is well suppressed up to the dying-off phase during chronological aging. We found that the leadoff of exogenous hydrogen peroxide induced genomic instability to viability significantly correlated with replicative lifespan (RLS), indicating that yeast cells’ ability to counter oxidative stress contributes to their replicative longevity. Surprisingly, this leadoff is positively correlated with an inverse measure of endogenous mitotic asymmetry, indicating a trade-off between mitotic asymmetry and cell’s ability to fend off hydrogen peroxide induced oxidative stress. Overall, our results demonstrate strong associations of oxidative stress to genomic instability and mitotic asymmetry at the population level of budding yeast.

scholarly journals Conserved Actin Cysteine Residues Are Oxidative Stress Sensors That Can Regulate Cell Death in Yeast

2007 ◽  
Vol 18 (4) ◽  
pp. 1359-1365 ◽  
Author(s):  
Michelle E. Farah ◽  
David C. Amberg
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Cellular Response ◽  
Yeast Cells ◽  
Nuclear Fragmentation ◽  
Actin Isoforms ◽  
Chronological Aging ◽  
Stress Sensors ◽  
Universal Mechanism ◽  
Regulate Cell Death

Actin's functional complexity makes it a likely target of oxidative stress but also places it in a prime position to coordinate the response to oxidative stress. We have previously shown that the NADPH oxidoreductase Oye2p protects the actin cytoskeleton from oxidative stress. Here we demonstrate that the physiological consequence of actin oxidation is to accelerate cell death in yeast. Loss of Oye2p leads to reactive oxygen species accumulation, activation of the oxidative stress response, nuclear fragmentation and DNA degradation, and premature chronological aging of yeast cells. The oye2Δ phenotype can be completely suppressed by removing the potential for formation of the actin C285-C374 disulfide bond, the likely substrate of the Oye2p enzyme or by treating the cells with the clinically important reductant N-acetylcysteine. Because these two cysteines are coconserved in all actin isoforms, we theorize that we have uncovered a universal mechanism whereby actin helps to coordinate the cellular response to oxidative stress by both sensing and responding to oxidative load.

scholarly journals MET18 Deficiency Increases the Sensitivity of Yeast to Oxidative Stress and Shortens Replicative Lifespan by Inhibiting Catalase Activity

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Ya-qin Chen ◽  
Xin-guang Liu ◽  
Wei Zhao ◽  
Hongjing Cui ◽  
Jie Ruan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Catalase Activity ◽  
Molecular Mechanisms ◽  
Cumene Hydroperoxide ◽  
Yeast Cells ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Replicative Capacity ◽  
Replicative Lifespan ◽  
Increased Sensitivity

Yeast MET18, a subunit of the cytosolic iron-sulfur (Fe/S) protein assembly (CIA) machinery which is responsible for the maturation of Fe/S proteins, has been reported to participate in the oxidative stress response. However, the underlying molecular mechanisms remain unclear. In this study, we constructed a MET18/met18Δ heterozygous mutant yeast strain and found that MET18 deficiency in yeast cells impaired oxidative stress resistance as evidenced by increased sensitivity to hydrogen peroxide (H2O2) and cumene hydroperoxide (CHP). Mechanistically, the mRNA levels of catalase A (CTA1) and catalase T (CTT1) as well as the total catalase activity were significantly reduced in MET18-deficient cells. In contrast, overexpression of CTT1 or CTA1 in MET18-deficient cells significantly increased the intracellular catalase activity and enhanced the resistance ability against H2O2 and CHP. In addition, MET18 deficiency diminished the replicative capacity of yeast cells as evidenced by the shortened replicative lifespan, which can be restored by CTT1 overexpression, but not by CTA1, in the MET18-deficient cells. These results suggest that MET18, in a catalase-dependent manner, plays an essential role in enhancing the resistance of yeast cells to oxidative stress and increasing the replicative capacity of yeast cells.

scholarly journals Candida albicans-Conditioned Medium Protects Yeast Cells from Oxidative Stress: a Possible Link between Quorum Sensing and Oxidative Stress Resistance

2005 ◽  
Vol 4 (10) ◽  
pp. 1654-1661 ◽  
Author(s):  
Caroline Westwater ◽  
Edward Balish ◽  
David A. Schofield
Keyword(s):  
Oxidative Stress ◽  
Hydrogen Peroxide ◽  
Candida Albicans ◽  
Stress Response ◽  
Quorum Sensing ◽  
Conditioned Medium ◽  
Oxidative Stress Response ◽  
Yeast Cells ◽  
Protective Response ◽  
Quorum Sensing Molecule

ABSTRACT Candida albicans, the most frequent fungal pathogen of humans, encounters high levels of oxidants following ingestion by professional phagocytes and through contact with hydrogen peroxide-producing bacteria. In this study, we provide evidence that C. albicans is able to coordinately regulate the oxidative stress response at the global cell population level by releasing protective molecules into the surrounding medium. We demonstrate that conditioned medium, which is defined as a filter-sterilized supernatant from a C. albicans stationary-phase culture, is able to protect yeast cells from both hydrogen peroxide and superoxide anion-generating agents. Exponential-phase yeast cells preexposed to conditioned medium were able to survive levels of oxidative stress that would normally kill actively growing yeast cells. Heat treatment, digestion with proteinase K, pH adjustment, or the addition of the oxidant scavenger alpha-tocopherol did not alter the ability of conditioned medium to induce a protective response. Farnesol, a heat-stable quorum-sensing molecule (QSM) that is insensitive to proteolytic enzymes and is unaffected by pH extremes, is partly responsible for this protective response. In contrast, the QSM tyrosol did not alter the sensitivity of C. albicans cells to oxidants. Relative reverse transcription-PCR analysis indicates that Candida-conditioned growth medium induces the expression of CAT1, SOD1, SOD2, and SOD4, suggesting that protection may be mediated through the transcriptional regulation of antioxidant-encoding genes. Together, these data suggest a link between the quorum-sensing molecule farnesol and the oxidative stress response in C. albicans.

Metal-based superoxide dismutase and catalase mimics reduce oxidative stress biomarkers and extend life span of Saccharomyces cerevisiae

2017 ◽  
Vol 474 (2) ◽  
pp. 301-315 ◽  
Author(s):  
Thales de P. Ribeiro ◽  
Fernanda L. Fonseca ◽  
Mariana D.C. de Carvalho ◽  
Rodrigo M. da C. Godinho ◽  
Fernando Pereira de Almeida ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Saccharomyces Cerevisiae ◽  
Superoxide Dismutase ◽  
Life Span ◽  
Yeast Cells ◽  
Cell Integrity ◽  
Oxidative Stress Biomarkers ◽  
Chronological Aging ◽  
Stress Biomarkers

Aging is a natural process characterized by several biological changes. In this context, oxidative stress appears as a key factor that leads cells and organisms to severe dysfunctions and diseases. To cope with reactive oxygen species and oxidative-related damage, there has been increased use of superoxide dismutase (SOD)/catalase (CAT) biomimetic compounds. Recently, we have shown that three metal-based compounds {[Fe(HPClNOL)Cl2]NO3, [Cu(HPClNOL)(CH3CN)](ClO4)2 and Mn(HPClNOL)(Cl)2}, harboring in vitro SOD and/or CAT activities, were critical for protection of yeast cells against oxidative stress. In this work, treating Saccharomyces cerevisiae with these SOD/CAT mimics (25.0 µM/1 h), we highlight the pivotal role of these compounds to extend the life span of yeast during chronological aging. Evaluating lipid and protein oxidation of aged cells, it becomes evident that these mimics extend the life expectancy of yeast mainly due to the reduction in oxidative stress biomarkers. In addition, the treatment of yeast cells with these mimics regulated the amounts of lipid droplet occurrence, consistent with the requirement and protection of lipids for cell integrity during aging. Concerning SOD/CAT mimics uptake, using inductively coupled plasma mass spectrometry, we add new evidence that these complexes, besides being bioabsorbed by S. cerevisiae cells, can also affect metal homeostasis. Finally, our work presents a new application for these SOD/CAT mimics, which demonstrate a great potential to be employed as antiaging agents. Taken together, these promising results prompt future studies concerning the relevance of administration of these molecules against the emerging aging-related diseases such as Parkinson's, Alzheimer's and Huntington's.

scholarly journals An aging-independent replicative lifespan in a symmetrically dividing eukaryote

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Eric C Spivey ◽  
Stephen K Jones ◽  
James R Rybarski ◽  
Fatema A Saifuddin ◽  
Ilya J Finkelstein
Keyword(s):  
Fission Yeast ◽  
Eukaryotic Cell ◽  
Quantitative Model ◽  
Cellular Aging ◽  
Yeast Cells ◽  
Replicative Lifespan ◽  
Processing Pipeline ◽  
Independent Mechanism ◽  
Genetic Perturbations ◽  
A Cell

The replicative lifespan (RLS) of a cell—defined as the number of cell divisions before death—has informed our understanding of the mechanisms of cellular aging. However, little is known about aging and longevity in symmetrically dividing eukaryotic cells because most prior studies have used budding yeast for RLS studies. Here, we describe a multiplexed fission yeast lifespan micro-dissector (multFYLM) and an associated image processing pipeline for performing high-throughput and automated single-cell micro-dissection. Using the multFYLM, we observe continuous replication of hundreds of individual fission yeast cells for over seventy-five generations. Surprisingly, cells die without the classic hallmarks of cellular aging, such as progressive changes in size, doubling time, or sibling health. Genetic perturbations and drugs can extend the RLS via an aging-independent mechanism. Using a quantitative model to analyze these results, we conclude that fission yeast does not age and that cellular aging and replicative lifespan can be uncoupled in a eukaryotic cell.

scholarly journals Buffering the pH of the culture medium does not extend yeast replicative lifespan

F1000Research ◽  
2013 ◽  
Vol 2 ◽  
pp. 216 ◽  
Author(s):  
Brian M Wasko ◽  
Daniel T Carr ◽  
Herman Tung ◽  
Ha Doan ◽  
Nathan Schurman ◽  
...  
Keyword(s):  
Life Span ◽  
Culture Medium ◽  
Synthetic Medium ◽  
Yeast Cells ◽  
Similar Process ◽  
Replicative Aging ◽  
Replicative Lifespan ◽  
Chronological Aging ◽  
Chronological Life Span ◽  
Initial Ph

During chronological aging of budding yeast cells, the culture medium can become acidified, and this acidification limits cell survival.  As a consequence, buffering the culture medium to pH 6 significantly extends chronological life span under standard conditions in synthetic medium.  In this study, we assessed whether a similar process occurs during replicative aging of yeast cells.  We find no evidence that buffering the pH of the culture medium to pH levels either higher or lower than the initial pH of the medium is able to significantly extend replicative lifespan.  Thus, we conclude that, unlike chronological life span, replicative life span is not limited by acidification of the culture medium or by changes in the pH of the environment.

scholarly journals An aging-independent replicative lifespan in a symmetrically dividing eukaryote

2016 ◽  
Author(s):  
Eric C. Spivey ◽  
Stephen K. Jones ◽  
James R. Rybarski ◽  
Fatema A. Saifuddin ◽  
Ilya J. Finkelstein
Keyword(s):  
Fission Yeast ◽  
Molecular Mechanisms ◽  
Single Cell Analysis ◽  
Eukaryotic Cell ◽  
Culture Conditions ◽  
Cellular Aging ◽  
Yeast Cells ◽  
Replicative Lifespan ◽  
A Cell ◽  
Defined Culture

AbstractThe replicative lifespan (RLS) of a cell—defined as the number of generations a cell divides before death—has informed our understanding of the molecular mechanisms of cellular aging. Nearly all RLS studies have been performed on budding yeast and little is known about the mechanisms of aging and longevity in symmetrically dividing eukaryotic cells. Here, we describe a multiplexed fission yeast (Schizosaccharomyces pombe) lifespan micro-dissector (FYLM); a microfluidic platform for performing automated micro-dissection and high-content single-cell analysis in well-defined culture conditions. Using the FYLM, we directly observe continuous and robust replication of hundreds of individual fission yeast cells for over seventy-five cell divisions. Surprisingly, cells die without any classic hallmarks of cellular aging such as changes in cell morphology, increased doubling time, or reduced sibling health. Genetic perturbations and longevity-enhancing drugs can further extend the replicative lifespan (RLS) via an aging-independent mechanism. We conclude that despite occasional sudden death of individual cells, fission yeast does not age. These results highlight that cellular aging and replicative lifespan can be uncoupled in a eukaryotic cell.

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