HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Mousavi, S. A. A. Articles by Robson, G. D. Search for Related Content PubMed PubMed Citation Articles by Mousavi, S. A. A. Articles by Robson, G. D. Agricola Articles by Mousavi, S. A. A. Articles by Robson, G. D.

Oxidative and amphotericin B-mediated cell death in the opportunistic pathogen Aspergillus fumigatus is associated with an apoptotic-like phenotype

School of Biological Sciences, 1.800 Stopford Building, University of Manchester, Manchester M13 9PT, UK

Correspondence
Geoffrey D. Robson
geoff.robson{at}man.ac.uk

When protoplasts of the opportunistic fungal pathogen Aspergillus fumigatus were treated with low but toxic levels of hydrogen peroxide (0·1 mM) or amphotericin B (0·5 µg ml^–1), loss of cell viability and death were associated with a number of phenotypic changes characteristic of apoptosis. The percentage of protoplasts staining positive with annexin V-FITC, an indicator of the externalization of phosphatidylserine and an early marker of apoptosis, rose to 55 % within 1 h. This was followed by a similar increase in apoptotic DNA fragmentation detected by the TUNEL assay, and led to a loss of cell permeability and death in 90 % of protoplasts, as indicated by the uptake of propidium iodide. The development of an apoptotic phenotype was blocked when protoplasts were pre-treated with the protein synthesis inhibitor cycloheximide, indicating active participation of the cell in the process. However, no significant activity against synthetic caspase substrates was detected, and the inclusion of the cell-permeant broad-spectrum caspase inhibitor Z-VAD-fmk did not block the development of the apoptotic-like phenotype. Higher concentrations of H₂O₂ (1·8 mM) and amphotericin B (1 µg ml^–1) caused protoplasts to die without inducing an apoptotic phenotype. As predicted, the fungistatic antifungal agent itraconazole, which inhibits growth without causing immediate cell death, did not induce an apoptotic-like phenotype.

This article has been cited by other articles:

				P. Gautam, J. Shankar, T. Madan, R. Sirdeshmukh, C. S. Sundaram, W. N. Gade, S. F. Basir, and P. U. Sarma Proteomic and Transcriptomic Analysis of Aspergillus fumigatus on Exposure to Amphotericin B Antimicrob. Agents Chemother., December 1, 2008; 52(12): 4220 - 4227. [Abstract] [Full Text] [PDF]

				A. Castro, C. Lemos, A. Falcao, N. L. Glass, and A. Videira Increased Resistance of Complex I Mutants to Phytosphingosine-induced Programmed Cell Death J. Biol. Chem., July 11, 2008; 283(28): 19314 - 19321. [Abstract] [Full Text] [PDF]

				C. P. Semighini, M. Savoldi, G. H. Goldman, and S. D. Harris Functional Characterization of the Putative Aspergillus nidulans Poly(ADP-Ribose) Polymerase Homolog PrpA Genetics, May 1, 2006; 173(1): 87 - 98. [Abstract] [Full Text] [PDF]

				C. Westwater, E. Balish, and D. A. Schofield Candida albicans-Conditioned Medium Protects Yeast Cells from Oxidative Stress: a Possible Link between Quorum Sensing and Oxidative Stress Resistance Eukaryot. Cell, October 1, 2005; 4(10): 1654 - 1661. [Abstract] [Full Text] [PDF]

				E. Leiter, H. Szappanos, C. Oberparleiter, L. Kaiserer, L. Csernoch, T. Pusztahelyi, T. Emri, I. Pocsi, W. Salvenmoser, and F. Marx Antifungal Protein PAF Severely Affects the Integrity of the Plasma Membrane of Aspergillus nidulans and Induces an Apoptosis-Like Phenotype Antimicrob. Agents Chemother., June 1, 2005; 49(6): 2445 - 2453. [Abstract] [Full Text] [PDF]