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N1-methylspermidine, a stable spermidine analog, prolongs anagen and regulates epithelial stem cell functions in human hair follicles

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Abstract

Spermidine (Spd), the prototypic polyamine, has been shown to be essential for hair follicle (HF) growth. However, Spd can be readily converted into other polyamines, and is physiologically unstable. Therefore, to assess its individual functions on HFs, we used the metabolically stable Spd analog N1-methylspermidine (N1-MeSpd). N1-MeSpd was confirmed to be a metabolically stable compound, with a half life of 90 h. 0.5 µM N1-MeSpd strongly prolonged anagen and decreased cell apoptosis in HFs in culture after 6 days, accompanied by specific stimulation of the expression of the epithelial stem cell-associated keratin, K15. N1-MeSpd also reduced lactate dehydrogenase activity in the culture supernatant, a parameter of cell death and cell lysis. N1-MeSpd diminished intracellular reactive oxygen species production in cultured keratinocytes, and reduced tumor necrosis factor-α, interleukin (IL)-1β and IL-6 gene and protein expression after lipopolysaccharide stimulation. This suggests that some effects of N1-MeSpd may be mediated by anti-oxidative and anti-inflammatory effects. These additional properties of N1-MeSpd could be clinically important for the treatment of inflammatory alopecias and inflammatory scalp diseases.

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Acknowledgments

The excellent technical assistance of Sylva Dürkop is gratefully appreciated. This study was supported in part by a basic research grant from Giuliani S.p.A., Milan, Italy, to R.P.

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Authors and Affiliations

  1. Department of Dermatology, Hadassah-Hebrew University Medical Center, PO Box 12000, 9112001, Jerusalem, Israel

    Yuval Ramot

  2. Giuliani S.p.A. R&D, Milan, Italy

    Barbara Marzani & Daniela Pinto

  3. Luebeck Institute of Experimental Dermatology, University of Luebeck, Luebeck, Germany

    Jennifer E. Kloepper

  4. Institute of Inflammation and Repair, University of Manchester, Manchester, UK

    Ralf Paus

  5. Department of Dermatology, University of Muenster, Muenster, Germany

    Ralf Paus

Authors
  1. Yuval Ramot
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  2. Barbara Marzani
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  3. Daniela Pinto
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  4. Jennifer E. Kloepper
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  5. Ralf Paus
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Correspondence to Yuval Ramot.

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Conflict of interest

Ralf Paus has received basic research grants from Giuliani S.p.A., Milan, Italy, and has served in a consultancy function for this company. Yuval Ramot has received travel support from Giuliani S.p.A. Barbara Marzani and Daniela Pinto are employed by Giuliani S.p.A.

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Ramot, Y., Marzani, B., Pinto, D. et al. N1-methylspermidine, a stable spermidine analog, prolongs anagen and regulates epithelial stem cell functions in human hair follicles. Arch Dermatol Res 307, 841–847 (2015). https://doi.org/10.1007/s00403-015-1592-9

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  • DOI: https://doi.org/10.1007/s00403-015-1592-9

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