| The human salivary peptide histatin 5 exerts its antifungal activity through the formation of reactive oxygen species. | |
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MedLine Citation:
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PMID: 11717389 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Previous studies have shown that the human salivary antifungal peptide histatin 5 is taken up by Candida albicans cells and associates intracellularly with mitochondria. The purpose of the present study was to investigate the biological consequence of this specific subcellular targeting. Histatin 5 inhibited respiration of isolated C. albicans mitochondria as well as the respiration of intact blastoconidia in a dose and time-dependent manner. A nearly perfect correlation was observed between histatin-induced inhibition of respiration and cell killing with either logarithmic- or stationary-phase cells, but stationary-phase cells were less sensitive. Because nonrespiring yeast cells are insensitive to histatin 5, the potential mechanistic relationship between histatin 5 interference with the respiratory apparatus and cell killing was explored by using an oxygen radical sensitive probe (dihydroethidium). Fluorimetric measurements showed that histatin 5 induced the formation of reactive oxygen species (ROS) in C. albicans cells as well as in isolated mitochondria and that ROS levels were highly correlated with cell death. In the presence of an oxygen scavenger (l-cysteine), cell killing and ROS formation were prevented. In addition, the membrane-permeant superoxide dismutase mimetic 2,2,6,6-tetramethylpiperidine-N-oxyl, abolished histatin-induced ROS formation in isolated mitochondria. In contrast to histatin 5, the conventional inhibitors of the respiratory chain, sodium cyanide or sodium azide, neither induced ROS nor killed yeast cells. These data provide strong evidence for a comprehensive mechanistic model of histatin-5-provoked yeast cell death in which oxygen radical formation is the ultimate and essential step. |
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Authors:
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E J Helmerhorst; R F Troxler; F G Oppenheim |
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Publication Detail:
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Type: Journal Article; Research Support, U.S. Gov't, P.H.S. Date: 2001-11-20 |
Journal Detail:
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Title: Proceedings of the National Academy of Sciences of the United States of America Volume: 98 ISSN: 0027-8424 ISO Abbreviation: Proc. Natl. Acad. Sci. U.S.A. Publication Date: 2001 Dec |
Date Detail:
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Created Date: 2001-12-05 Completed Date: 2002-01-10 Revised Date: 2009-11-18 |
Medline Journal Info:
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Nlm Unique ID: 7505876 Medline TA: Proc Natl Acad Sci U S A Country: United States |
Other Details:
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Languages: eng Pagination: 14637-42 Citation Subset: IM |
Affiliation:
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Department of Periodontology and Oral Biology, Boston University Goldman School of Dental Medicine, 100 East Newton Street, Boston, MA 02118-2392, USA. helmer@bu.edu |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Amino Acid Sequence Antifungal Agents / chemistry, pharmacology* Candida albicans / drug effects*, metabolism* Histatins Humans Mitochondria / drug effects, metabolism Models, Biological Molecular Sequence Data Oxygen Consumption / drug effects Reactive Oxygen Species / metabolism* Salivary Proteins and Peptides / chemistry, pharmacology* |
| Grant Support | |
ID/Acronym/Agency:
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DE05672/DE/NIDCR NIH HHS; DE07652/DE/NIDCR NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antifungal Agents; 0/HTN3 protein, human; 0/Histatins; 0/Reactive Oxygen Species; 0/Salivary Proteins and Peptides |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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