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The antipsoriatic drug metabolite etretin (Ro 10-1670) alters the metabolism of fatty acids in human keratinocytes in culture

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Summary

We have studied the effect of etretin (Ro 10-1670), the active metabolite of the widely used antipsoriatic drug etretinate (Ro 10-9359), on the incorporation and release of arachidonic acid in human skin keratinocytes. During 24-h culture, radioactive 14C-arachidonic acid was avidly incorporated into the cellular lipids of the keratinocytes. When the cells were cultured for another 48 h in fresh medium, 8.8%±0.3% of the incorporated radioactivity was released from the cells. The presence of etretin (10-8 M to 10-5 M) in the medium stimulated the release of radiolabel. With 10-5 M etretin in the culture medium, 13.0%±0.4% of the incorporated radioactivity was released, and this was accompanied by decreased labelling of phosphatidylethanolamine. This suggests that phosphatidylethanolamine may be an important source of the released arachidonic acid.

Etretin pretreatment reduced the incorporation of 14C-arachidonic acid into diacylglycerols, triacylglycerols, and cholesteryl esters. Pretreatment for 48 h with 10-5 M etretin reduced subsequent 14C-arachidonic acid incorporation into nonphosphorus lipids from a mean total of 8.2%±0.2% to 3.2%±0.1% (p<0.001). These findings suggest that etretin interferes with the esterification of arachidonic acid into nonphosphorus lipids. Etretin was also found to cause changes in the fatty acid composition of keratinocytes. Following 48 h culture with etretin, the percentage amount of the fatty acids belonging to the n3 series was increased whereas that of palmitic acid (16:0) and palmitoleic acid (16:1n7) was decreased. In conclusion, our study suggests that etretin in therapeutical concentrations affects fatty acid metabolism in human keratinocytes in culture.

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Authors and Affiliations

  1. Department of Physiology, University of Turku, SF-20520, Turku 52, Finland

    K. Punnonen

  2. Department of Dermatology, University of Turku, SF-20520, Turku 52, Finland

    C. T. Jansén

  3. Department of Physiological Chemistry, Karolinska Institutet, S-10401, Stockholm, Sweden

    T. Puustinen

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  1. K. Punnonen
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  2. T. Puustinen
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  3. C. T. Jansén
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Punnonen, K., Puustinen, T. & Jansén, C.T. The antipsoriatic drug metabolite etretin (Ro 10-1670) alters the metabolism of fatty acids in human keratinocytes in culture. Arch Dermatol Res 280, 103–107 (1988). https://doi.org/10.1007/BF00417713

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  • DOI: https://doi.org/10.1007/BF00417713

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