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

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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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Acknowledgments

This work was supported by a grant from the NIH (R01 GM57945). The support of the Georgia Research Alliance is also gratefully acknowledged.

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Authors and Affiliations

  1. Department of Biology, Georgia State University, 24 Peachtree Center Avenue, Atlanta, GA, 30303, USA

    Amrita M. Nargund & John E. Houghton

  2. School of Biology, University of Nottingham, University Park, Nottingham, NG7 2RD, UK

    Simon V. Avery

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  1. Amrita M. Nargund
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Correspondence to John E. Houghton.

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Nargund, A.M., Avery, S.V. & Houghton, J.E. Cadmium induces a heterogeneous and caspase-dependent apoptotic response in Saccharomyces cerevisiae . Apoptosis 13, 811–821 (2008). https://doi.org/10.1007/s10495-008-0215-8

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