Valproic acid induces apoptosis dependent of Yca1p at concentrations that mildly affect the proliferation of yeast

Edited by Francesc Posas

Received 27 September 2004; received in revised form 20 December 2004; accepted 21 December 2004. published online 10 January 2005.

Abstract

Valproic acid (VPA) inhibited the growth of yeast in a dose-dependent manner with complete inhibition attained at 100mM. When cells were exposed to 25mM VPA, the wild-type died showing apoptotic markers, while yca1Δ deleted of YCA1 encoding yeast caspase 1 survived. On the other hand, when cells were exposed to 50mM VPA, both the wild-type and yca1Δ died showing morphological features similar to those of the autophagic death of cdc28 which was also independent of YCA1. Thus, these results suggested that yeast cells die via YCA1-dependent apoptosis when their proliferative activity is mildly impaired.

Keywords: Budding yeast, Apoptosis, Caspase, Autophagic death, Valproate, Reactive oxygen species

Abbreviations: VPA, valproic acid, PCR, polymerase chain reaction, TUNEL, terminal deoxynucleotidyl transferase-mediated dUTP nick-end-labeling, ROS, reactive oxygen species

University of Yamanashi, Faculty of Medicine, Department of Biochemistry 2, 1110 Shimokato, Tamaho, Nakakoma, Yamanashi 409-3898, Japan

Corresponding author. Fax: +81 055 273 6784

PII: S0014-5793(05)00006-2

doi:10.1016/j.febslet.2004.12.051

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