Cadmium induces a heterogeneous and caspase-dependent apoptotic response in Saccharomyces cerevisiae

“…Manganese is also an inducer of mitochondriondependent apoptosis, but contrary to copper, apoptotic death by manganese depends on Yca1p and does not correlate with intracellular ROS accumulation (Liang & Zhou, 2007). Low cadmium concentrations induce Yca1p-dependent apoptosis in S. cerevisiae, probably as a consequence of intracellular GSH depletion and redox imbalance (Gomes et al, 2008;Nargund et al, 2008). Arsenite also causes glutathione depletion and Yca1-and mitochondriondependent apoptosis in yeast cells (Du et al, 2007 Recently, it has been reported that an S. cerevisiae mutant lacking Grx1p and Grx2p shows increased growth sensitivity to selenite (Lewinska & Bartosz, 2008).…”

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confidence: 99%

Selenite-induced cell death in Saccharomyces cerevisiae: protective role of glutaredoxins

2010

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Unlike in higher organisms, selenium is not essential for growth in Saccharomyces cerevisiae. In this species, it causes toxic effects at high concentrations. In the present study, we show that when supplied as selenite to yeast cultures growing under fermentative metabolism, its effects can be dissected into two death phases. From the time of initial treatment, it causes loss of membrane integrity and genotoxicity. Both effects occur at higher levels in mutants lacking Grx1p and Grx2p than in wild-type cells, and are reversed by expression of a cytosolic version of the membrane-associated Grx7p glutaredoxin. Grx7p can also rescue the high levels of protein carbonylation damage that occur in selenite-treated cultures of the grx1 grx2 mutant. After longer incubation times, selenite causes abnormal nuclear morphology and the appearance of TUNELpositive cells, which are considered apoptotic markers in yeast cells. This effect is independent of Grx1p and Grx2p. Therefore, the protective role of the two glutaredoxins is restricted to the initial stages of selenite treatment. Lack of Yca1p metacaspase or of a functional mitochondrial electron transport chain only moderately diminishes apoptotic-like death by selenite. In contrast, seleniteinduced apoptosis is dependent on the apoptosis-inducing factor Aif1p. In the absence of the latter, intracellular protein carbonylation is reduced after prolonged selenite treatment, supporting the supposition that part of the oxidative damage is contributed by apoptotic cells. INTRODUCTIONSelenium (Se) is a trace element which may have anticarcinogenic action at low concentrations (Letavayová et al., 2006). The essential character of Se in the mammalian diet is related to its presence as selenocysteine in a number of selenoproteins, such as thioredoxin reductases and glutathione peroxidases (Lu & Holmgren, 2009). These enzymes act in the defence against oxidative stress. In contrast, at high concentrations, Se is toxic because it generates oxidative stress and provokes DNA damage (Hatfield et al., 2006;Letavayová et al., 2006). Among the Se compounds that may come into contact with cells, selenite is a prooxidant because it undergoes glutathionemediated reduction to hydrogen selenide with the subsequent formation of superoxide radicals, which can undergo conversion into other reactive oxygen species (ROS) Spallholz, 1997;Tarze et al., 2007). Saccharomyces cerevisiae is a suitable organism to study the toxic properties of Se and the cellular mechanisms which prevent or repair its effects, without the interference due to an Se requirement for selenoproteins. In fact, S. cerevisiae, and fungi in general, do not contain selenoproteins and therefore Se is not essential for these organisms (Lu & Holmgren, 2009). High concentrations of Se cause DNA double-strand breaks in exponentially growing S. cerevisiae cells (Letavayová et al., 2008) and RAD9-dependent cell cycle arrest (Pinson et al., 2000). Accordingly, yeast mutants defective in the RAD9-mediated DNA repair pathway or the RAD6/RAD...

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“…It has been shown that metals like Cu and Mn are beneficial for yeast cells at subtoxic levels; however, both metals induced apoptosis in yeast cells at moderate toxic levels, while at even higher concentrations necrosis takes over (Liang and Zhou 2007). Similarly, Cd, at low concentrations, induces apoptosis in yeast cells (Nargund et al 2008). These data, associated with the findings described above about the loss of cell proliferation capacity in the absence of the injury of cell membrane, prompted us to investigate other characteristic apoptotic phenotype markers in Pb-exposed cells.…”

Section: Discussionmentioning

confidence: 99%

“…and hydrogen peroxide (H 2 O 2 ), are usually produced during aerobic metabolism (Jamieson 1998). ROS can also be intracellularly accumulated by exposition of cells to ionic radiations (Jamieson 1998) to heavy metals such as Cu or Cd (Shanmuganathan et al 2004;Liang and Zhou 2007;Nargund et al 2008). ROS formation originates different harmful effects, which includes the lipids peroxidation (Howlett and Avery 1997) and proteins oxidation (Shanmuganathan et al 2004;Sumner et al 2005).…”

Section: Introductionmentioning

confidence: 99%

“…Yeast cell death by apoptosis is accompanied by diagnostic features resembling those observed in mammalian cells such as exposition of phosphatidylserine, DNA fragmentation and chromatin condensation in the absence of the loss of cell membrane integrity (Madeo et al 1997(Madeo et al , 2009). In yeast cells, several apoptosis inducers have been described such as hydrogen peroxide (Madeo et al 1999), acetic acid (Ludovico et al 2001), sugar (Granot et al 2003), aspirin (Balzan et al 2004), chronological and replicative ageing (Rockenfeller and Madeo 2008) and metals like Cd (Nargund et al 2008), Cu and Mn (Liang and Zhou 2007).…”

Section: Introductionmentioning

confidence: 99%

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Lead induces oxidative stress and phenotypic markers of apoptosis in Saccharomyces cerevisiae

Bussche

Soares

2010

Appl Microbiol Biotechnol

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In the present work, the mode of cell death induced by Pb in Saccharomyces cerevisiae was studied. Yeast cells Pb-exposed, up to 6 h, loss progressively the capacity to proliferate and maintained the membrane integrity evaluated by the fluorescent probes bis(1,3-dibutylbarbituric acid trimethine oxonol) and propidium iodide. Pb-induced death is an active process, requiring the participation of cellular metabolism, since the simultaneous addition of cycloheximide attenuated the loss of cell proliferation capacity. Cells exposed to Pb accumulated intracelullarly reactive oxygen species (ROS), evaluated by 2′,7′-dichlorodihydrofluorescein diacetate. The addition of ascorbic acid (a ROS scavenger) strongly reduced the oxidative stress and impaired the loss of proliferation capacity in Pb-treated cells. Pb-exposed cells displayed nuclear morphological alterations, like chromatin fragmentation, as revealed by diaminophenylindole staining. Together, the data obtained indicate that yeast cells exposition to 1 mmol/l Pb results in severe oxidative stress which can be the trigger of programmed cell death by apoptosis.

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Cadmium induces a heterogeneous and caspase-dependent apoptotic response in Saccharomyces cerevisiae

Cited by 48 publications

References 77 publications

Identification of autophagy genes participating in zinc-induced necrotic cell death inSaccharomyces cerevisiae

Identification of autophagy genes participating in zinc-induced necrotic cell death inSaccharomyces cerevisiae

Selenite-induced cell death in Saccharomyces cerevisiae: protective role of glutaredoxins

Lead induces oxidative stress and phenotypic markers of apoptosis in Saccharomyces cerevisiae

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