PMID- 17233764 OWN - NLM STAT- MEDLINE DCOM- 20070614 LR - 20220409 IS - 1567-1356 (Print) IS - 1567-1356 (Linking) VI - 7 IP - 3 DP - 2007 May TI - An atypical active cell death process underlies the fungicidal activity of ciclopirox olamine against the yeast Saccharomyces cerevisiae. PG - 404-12 AB - Ciclopirox olamine (CPO), a fungicidal agent widely used in clinical practice, induced in Saccharomyces cerevisiae an active cell death (ACD) process characterized by changes in nuclear morphology and chromatin condensation associated with the appearance of a population in the sub-G(0)/G(1) cell cycle phase and an arrest delay in the G(2)/M phases. This ACD was associated neither with intracellular reactive oxygen species (ROS) signaling, as revealed by the use of different classes of ROS scavengers, nor with a terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)-positive phenotype. Furthermore, CPO-induced cell death seems to be dependent on unknown protease activity but independent of the apoptotic regulators Aif1p and Yca1p and of autophagic pathways involving Apg5p, Apg8p and Uth1p. Our results show that CPO triggers in S. cerevisiae an atypical nonapoptotic, nonautophagic ACD with as yet unknown regulators. FAU - Almeida, Bruno AU - Almeida B AD - Life and Health Sciences Research Institute (ICVS), Health Sciences School, University of Minho, Campus de Gualtar, Braga, Portugal. FAU - Sampaio-Marques, Belem AU - Sampaio-Marques B FAU - Carvalho, Joana AU - Carvalho J FAU - Silva, Manuel T AU - Silva MT FAU - Leao, Cecilia AU - Leao C FAU - Rodrigues, Fernando AU - Rodrigues F FAU - Ludovico, Paula AU - Ludovico P LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20070119 PL - England TA - FEMS Yeast Res JT - FEMS yeast research JID - 101085384 RN - 0 (Antifungal Agents) RN - 0 (Free Radical Scavengers) RN - 0 (Protein Synthesis Inhibitors) RN - 0 (Pyridones) RN - 0 (Reactive Oxygen Species) RN - 19W019ZDRJ (Ciclopirox) RN - 98600C0908 (Cycloheximide) RN - EC 3.4.23.- (Aspartic Acid Endopeptidases) SB - IM MH - Antifungal Agents/*pharmacology MH - Aspartic Acid Endopeptidases/metabolism MH - Cell Cycle/drug effects/physiology MH - Cell Membrane/drug effects/physiology MH - Ciclopirox MH - Cycloheximide/pharmacology MH - Flow Cytometry MH - Free Radical Scavengers/pharmacology MH - In Situ Nick-End Labeling MH - Kinetics MH - Microscopy, Electron, Transmission MH - Mitochondrial Membranes/drug effects/physiology MH - Protein Synthesis Inhibitors/pharmacology MH - Pyridones/*pharmacology MH - Reactive Oxygen Species/metabolism MH - Saccharomyces cerevisiae/*cytology/*drug effects/growth & development/metabolism EDAT- 2007/01/20 09:00 MHDA- 2007/06/15 09:00 CRDT- 2007/01/20 09:00 PHST- 2007/01/20 09:00 [pubmed] PHST- 2007/06/15 09:00 [medline] PHST- 2007/01/20 09:00 [entrez] AID - FYR188 [pii] AID - 10.1111/j.1567-1364.2006.00188.x [doi] PST - ppublish SO - FEMS Yeast Res. 2007 May;7(3):404-12. doi: 10.1111/j.1567-1364.2006.00188.x. Epub 2007 Jan 19.