The Penicillium chrysogenum-derived antifungal peptide shows no toxic effects on mammalian cells in the intended therapeutic concentration

Henrietta Szappanos, G. Szigeti, B. Pál, Zoltán Rusznák, G. Szücs, E. Rajnavolgyi, J. Balla, G. Balla, E. Nagy, E. Leiter, I. Pócsi, Florentine Marx, L. Csernoch

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27 Citations (Scopus)

Abstract

Certain filamentous fungi, such as the penicillin-producing strain Penicillium chrysogenum, secrete small, highly basic and cysteine-rich proteins with antifungal effects. Affected fungi include a number of important zoopathogens, including those infecting humans. Recent studies, however, have pointed to a membrane-perturbing effect of these antifungal compounds, apparent as a potassium efflux from affected fungal cells. If present on mammalian cells, this would severely hinder the potential therapeutic use of these molecules. Here we studied the effects of the P. chrysogenum-derived antifungal peptide (PAF) on a number of mammalian cells to establish whether the protein has any cytotoxic effects, alters transmembrane currents on excitable cells or activates the immune system. PAF, in a concentration range of 2-100 μg/ml, did not cause any cytotoxicity on human endothelial cells from the umbilical vein. Applied at 10 μg/ml, it also failed to modify voltage-gated potassium channels of neurones, skeletal muscle fibers, and astrocytes. PAF also left the hyperpolarization-activated non-specific cationic current (Ih) and the L-type calcium current unaffected. Finally, up to 2 μg/ml, PAF did not induce the production of pro-inflammatory cytokines such as IL-6, IL-8, and TNF-α. These results suggest that PAF should have only minor, if any, effects on mammalian cells in the intended therapeutic concentration range.

Original languageEnglish
Pages (from-to)122-132
Number of pages11
JournalNaunyn-Schmiedeberg's Archives of Pharmacology
Volume371
Issue number2
DOIs
Publication statusPublished - Feb 2005

Fingerprint

Penicillium chrysogenum
Poisons
Peptides
Fungi
Voltage-Gated Potassium Channels
Skeletal Muscle Fibers
Human Umbilical Vein Endothelial Cells
Therapeutic Uses
Therapeutics
Interleukin-8
Astrocytes
Penicillins
Cysteine
Immune System
Interleukin-6
Potassium
Proteins
Cell Count
Cytokines
Calcium

Keywords

  • Antifungal proteins
  • Calcium current
  • Cytotoxicity
  • Inflammatory action
  • Patch clamp
  • Potassium current

ASJC Scopus subject areas

  • Pharmacology

Cite this

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abstract = "Certain filamentous fungi, such as the penicillin-producing strain Penicillium chrysogenum, secrete small, highly basic and cysteine-rich proteins with antifungal effects. Affected fungi include a number of important zoopathogens, including those infecting humans. Recent studies, however, have pointed to a membrane-perturbing effect of these antifungal compounds, apparent as a potassium efflux from affected fungal cells. If present on mammalian cells, this would severely hinder the potential therapeutic use of these molecules. Here we studied the effects of the P. chrysogenum-derived antifungal peptide (PAF) on a number of mammalian cells to establish whether the protein has any cytotoxic effects, alters transmembrane currents on excitable cells or activates the immune system. PAF, in a concentration range of 2-100 μg/ml, did not cause any cytotoxicity on human endothelial cells from the umbilical vein. Applied at 10 μg/ml, it also failed to modify voltage-gated potassium channels of neurones, skeletal muscle fibers, and astrocytes. PAF also left the hyperpolarization-activated non-specific cationic current (Ih) and the L-type calcium current unaffected. Finally, up to 2 μg/ml, PAF did not induce the production of pro-inflammatory cytokines such as IL-6, IL-8, and TNF-α. These results suggest that PAF should have only minor, if any, effects on mammalian cells in the intended therapeutic concentration range.",
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AU - Szappanos, Henrietta

AU - Szigeti, G.

AU - Pál, B.

AU - Rusznák, Zoltán

AU - Szücs, G.

AU - Rajnavolgyi, E.

AU - Balla, J.

AU - Balla, G.

AU - Nagy, E.

AU - Leiter, E.

AU - Pócsi, I.

AU - Marx, Florentine

AU - Csernoch, L.

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