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The Bacterial Peptide Pheromone Plantaricin A Permeabilizes Cancerous, but not Normal, Rat Pituitary Cells and Differentiates between the Outer and Inner Membrane Leaflet

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Abstract

Plantaricin A (PlnA) is a 26-mer peptide pheromone with membrane-permeabilizing, strain-specific antibacterial activity, produced by Lactobacillus plantarum C11. We investigated the membrane-permeabilizing effects of PlnA on cultured cancerous and normal rat anterior pituitary cells using patch-clamp techniques and microfluorometry (fura-2). Cancerous cells displayed massive permeabilization within 5 s after exposure to 10–100 μm PlnA. The membrane depolarized to nearly 0 mV, and the membrane resistance decreased to a mere fraction of the initial value after less than 1 min. In outside-out membrane patches, 10 μm PlnA induced membrane currents reversing at 0 mV, which is compatible with an unspecific conductance increase. The d and l forms of the peptide had similar potency, indicating a nonchiral mechanism for the membrane-permeabilizing effect. Surprisingly, inside-out patches were insensitive to 1 mm PlnA. Primary cultures of normal rat anterior pituitary cells were also insensitive to the peptide. Thus, PlnA differentiates between plasma membranes and membrane leaflets. Microfluorometric recordings of [Ca2+] i and cytosolic concentration of fluorochrome verified the rapid permeabilizing effect of PlnA on cancerous cells and the insensitivity of normal pituitary cells.

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Acknowledgements

This work was supported by grants from the Norwegian Research Council. We thank Gunnar Fimland for help in preparing PlnA and Jørgen Jensen for providing the rat pituitaries used for the primary cultures.

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  1. Department of Molecular Biosciences, University of Oslo, NO, 0316, Oslo, Norway

    Sverre L. Sand, Trude M. Haug, Jon Nissen-Meyer & Olav Sand

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  1. Sverre L. Sand
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Correspondence to Olav Sand.

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Sand, S.L., Haug, T.M., Nissen-Meyer, J. et al. The Bacterial Peptide Pheromone Plantaricin A Permeabilizes Cancerous, but not Normal, Rat Pituitary Cells and Differentiates between the Outer and Inner Membrane Leaflet. J Membrane Biol 216, 61–71 (2007). https://doi.org/10.1007/s00232-007-9030-3

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