Cadmium induces a heterogeneous and caspase-dependent apoptotic response in <Emphasis Type="Italic">Saccharomyces cerevisiae</Emphasis> |
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Authors: | Amrita M Nargund Simon V Avery John E Houghton |
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Institution: | (1) Department of Biology, Georgia State University, 24 Peachtree Center Avenue, Atlanta, GA 30303, USA;(2) School of Biology, University of Nottingham, University Park, Nottingham, NG7 2RD, UK |
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Abstract: | The toxic metal cadmium is linked to a series of degenerative disorders in humans, in which Cd-induced programmed cell death
(apoptosis) may play a role. The yeast, Saccharomyces cerevisiae, provides a valuable model for elucidating apoptosis mechanisms, and this study extends that capability to Cd-induced apoptosis.
We demonstrate that S. cerevisiae undergoes a glucose-dependent, programmed cell death in response to low cadmium concentrations, which is initiated within
the first hour of Cd exposure. The response was associated with induction of the yeast caspase, Yca1p, and was abolished in
a yca1Δ mutant. Cadmium-dependent apoptosis was also suppressed in a gsh1Δ mutant, indicating a requirement for glutathione. Other apoptotic markers, including sub-G1 DNA fragmentation and hyper-polarization of mitochondrial membranes, were also evident among Cd-exposed cells. These responses
were not distributed uniformly throughout the cell population, but were restricted to a subset of cells. This apoptotic subpopulation
also exhibited markedly elevated levels of intracellular reactive oxygen species (ROS). The heightened ROS levels alone were
not sufficient to induce apoptosis. These findings highlight several new perspectives to the mechanism of Cd-dependent apoptosis
and its phenotypic heterogeneity, while opening up future analyses to the power of the yeast model system. |
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Keywords: | Cadmium Yeast Mitochondrial membrane hyperpolarization-apoptosis Heterogeneity |
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