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Structure—activity relationship of porphyrin-induced photoinactivation with membrane function in bacteria and erythrocytes

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Abstract

We analyzed the structure–activity relationship of porphyrins with the photoinactivation of membrane function in bacteria and erythrocytes. The porphyrins tested were protoporphyrin (PP), mesoporphyrin (MP), deuteroporphyrin (DP), hematoporphyrin (HP), coproporphyrin (CP) and uroporphyrin (UP), along with hematoporphyrin derivative (HPD) and photofrin (PF). These porphyrins dissipated membrane potential of Staphylococcus aureus cells depending on the degrees of respiratory inhibition and K+ leakage. The dysfunction of bacterial membrane was caused within minutes and in the order of PP ~ MP > DP > HPD ≫ HP > PF > CP ~ UP. For bovine erythrocytes, these porphyrins induced leakage of K+ and inhibition of the enzyme acetylcholinesterase, which is located on the outer layer of the erythrocyte membrane, in the same order as that observed in bacteria. At high concentrations of PP, MP, DP and HPD, hemolysis (the lysis of erythrocytes with liberation of hemoglobin) was also induced. We found that the degree of photoinactivation of membrane function was closely associated with porphyrin-induced morphological changes in bovine erythrocytes, forming a crenated form from the normal discoid, which is the index of the amount of porphyrins in the outer layer of the cytoplasmic membrane. Furthermore, the degree of morphological changes was related with the octanol/water partition coefficients of porphyrins. These results strongly supported that porphyrins located in the outer layer of cytoplasmic membrane inactivated the cell membrane function by photo-irradiation, and the strength of photoinactivation by porphyrins depended on their affinity to the cell membrane.

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Acknowledgements

We thank Ms Kana Miyamoto who carried out some of the preliminary experiments that were extended in this study. We are grateful to Ms Yuka Nakanishi for technical assistance. This work was supported by a Grant-in-Aid for Scientific Research (KAKENHI 25460036) from the Japan Society for the Promotion of Science.

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Authors and Affiliations

  1. School of Pharmacy, Shujitsu University, 1-6-1 Nishigawara, Naka-ku, Okayama-shi, Okayama, 703-8516, Japan

    Hisato Kato & Takashi Katsu

  2. Faculty of Pharmaceutical Sciences, Okayama University, 1-1-1, Tsushimanaka, Kita-ku, Okayama-shi, Okayama, 700-8530, Japan

    Keiko Komagoe

  3. Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 1-1-1, Tsushimanaka, Kita-ku, Okayama-shi, Okayama, 700-8530, Japan

    Tsuyoshi Inoue

  4. Graduate School of Clinical Pharmacy, Shujitsu University, 1-6-1 Nishigawara, Naka-ku, Okayama-shi, Okayama, 703-8516, Japan

    Kazufumi Masuda

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  1. Hisato Kato
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  3. Tsuyoshi Inoue
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  4. Kazufumi Masuda
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Correspondence to Hisato Kato.

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Kato, H., Komagoe, K., Inoue, T. et al. Structure—activity relationship of porphyrin-induced photoinactivation with membrane function in bacteria and erythrocytes. Photochem Photobiol Sci 17, 954–963 (2018). https://doi.org/10.1039/c8pp00092a

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