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

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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. © 1995.

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Haimovich, B., & Tanaka, J. C. (1995). Magainin-induced cytotoxicity in eukaryotic cells: kinetics, dose-response and channel characteristics. BBA - Biomembranes, 1240(2), 149–158. https://doi.org/10.1016/0005-2736(95)00204-9

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