Magainin-induced cytotoxicity in eukaryotic cells: kinetics, dose-response and channel characteristics

Beatrice Haimovich, Jacqueline C. Tanaka

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Magainin 1 and magainin 2 are broad-spectrum antimicrobial and antifungal peptides initially purified from Xenopus laevis skin glands. The mechanism of cytotoxicity of the naturally occurring magainin 2 and a potent all-D amino acid analogue, MSI-238, was examined for eukaryotic cells using flow cytometric analysis with propidium iodide (PI). Exposure to MSI-238 resulted in cell death within seconds to minutes, depending on the concentration of the peptide. Several cell types were examined including a mouse fibroblast cell line Balb/3T3 and a Rous sarcoma virus Balb/3T3-transformed cell line, SRD/3T3, primary chick embryo fibroblasts and cells derived from a human ovarian carcinoma, OVCA-3. The K0.5 values determined from 5 min exposures ranged from 24 to 80 μg/ml for MSI-238 and ∼ 600 μg/ml for magainin 2. Molecular properties of MSI-238 induced channels were studied in excised membrane patch recordings from Balb/3T3 and SRD/3T3 cells. At low concentrations of 0.1 μg/ml, occasional, brief, multiple-level current fluctuations were seen suggesting channels with multiple, rapidly changing conductance levels. At 5 or 10 μg/ml of MSI-238, the current fluctuations were larger in magnitude and occurred more frequently producing a general disruption of the membrane similar to the effects of melittin on membranes.

Original languageEnglish (US)
Pages (from-to)149-158
Number of pages10
JournalBBA - Biomembranes
Volume1240
Issue number2
DOIs
StatePublished - Dec 13 1995

Fingerprint

Magainins
Eukaryotic Cells
Cytotoxicity
Kinetics
3T3 Cells
Fibroblasts
Membranes
Cells
Melitten
Rous sarcoma virus
Peptides
Transformed Cell Line
Propidium
Xenopus laevis
Cell death
Chick Embryo
Viruses
Skin
Cell Death
N-methylsuccinimide

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Cell Biology

Keywords

  • Anti-microbial peptide
  • Cytolysis
  • Eukaryotic cell
  • Flow cytometry
  • Ion channel
  • Magainin peptide
  • Propidium iodide

Cite this

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abstract = "Magainin 1 and magainin 2 are broad-spectrum antimicrobial and antifungal peptides initially purified from Xenopus laevis skin glands. The mechanism of cytotoxicity of the naturally occurring magainin 2 and a potent all-D amino acid analogue, MSI-238, was examined for eukaryotic cells using flow cytometric analysis with propidium iodide (PI). Exposure to MSI-238 resulted in cell death within seconds to minutes, depending on the concentration of the peptide. Several cell types were examined including a mouse fibroblast cell line Balb/3T3 and a Rous sarcoma virus Balb/3T3-transformed cell line, SRD/3T3, primary chick embryo fibroblasts and cells derived from a human ovarian carcinoma, OVCA-3. The K0.5 values determined from 5 min exposures ranged from 24 to 80 μg/ml for MSI-238 and ∼ 600 μg/ml for magainin 2. Molecular properties of MSI-238 induced channels were studied in excised membrane patch recordings from Balb/3T3 and SRD/3T3 cells. At low concentrations of 0.1 μg/ml, occasional, brief, multiple-level current fluctuations were seen suggesting channels with multiple, rapidly changing conductance levels. At 5 or 10 μg/ml of MSI-238, the current fluctuations were larger in magnitude and occurred more frequently producing a general disruption of the membrane similar to the effects of melittin on membranes.",
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Magainin-induced cytotoxicity in eukaryotic cells : kinetics, dose-response and channel characteristics. / Haimovich, Beatrice; Tanaka, Jacqueline C.

In: BBA - Biomembranes, Vol. 1240, No. 2, 13.12.1995, p. 149-158.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Magainin-induced cytotoxicity in eukaryotic cells

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AU - Haimovich, Beatrice

AU - Tanaka, Jacqueline C.

PY - 1995/12/13

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AB - Magainin 1 and magainin 2 are broad-spectrum antimicrobial and antifungal peptides initially purified from Xenopus laevis skin glands. The mechanism of cytotoxicity of the naturally occurring magainin 2 and a potent all-D amino acid analogue, MSI-238, was examined for eukaryotic cells using flow cytometric analysis with propidium iodide (PI). Exposure to MSI-238 resulted in cell death within seconds to minutes, depending on the concentration of the peptide. Several cell types were examined including a mouse fibroblast cell line Balb/3T3 and a Rous sarcoma virus Balb/3T3-transformed cell line, SRD/3T3, primary chick embryo fibroblasts and cells derived from a human ovarian carcinoma, OVCA-3. The K0.5 values determined from 5 min exposures ranged from 24 to 80 μg/ml for MSI-238 and ∼ 600 μg/ml for magainin 2. Molecular properties of MSI-238 induced channels were studied in excised membrane patch recordings from Balb/3T3 and SRD/3T3 cells. At low concentrations of 0.1 μg/ml, occasional, brief, multiple-level current fluctuations were seen suggesting channels with multiple, rapidly changing conductance levels. At 5 or 10 μg/ml of MSI-238, the current fluctuations were larger in magnitude and occurred more frequently producing a general disruption of the membrane similar to the effects of melittin on membranes.

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