title: N(1)-methylspermidine, a stable spermidine analog, prolongs anagen and regulates epithelial stem cell functions in human hair follicles.
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 N(1)-methylspermidine (N(1)-MeSpd). N(1)-MeSpd was confirmed to be a metabolically stable compound, with a half life of 90 h. 0.5 µM N(1)-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. N(1)-MeSpd also reduced lactate dehydrogenase activity in the culture supernatant, a parameter of cell death and cell lysis. N(1)-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 N(1)-MeSpd may be mediated by anti-oxidative and anti-inflammatory effects. These additional properties of N(1)-MeSpd could be clinically important for the treatment of inflammatory alopecias and inflammatory scalp diseases.
authors.affiliation: Department of Dermatology, Hadassah-Hebrew University Medical Center, PO Box 12000, 9112001, Jerusalem, Israel. yramot@gmail.com.
authors.forename: Yuval
authors.initials: Y
authors.lastname: Ramot
authors.affiliation: Giuliani S.p.A. R&D, Milan, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Marzani
authors.affiliation: Giuliani S.p.A. R&D, Milan, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Pinto
authors.affiliation: Luebeck Institute of Experimental Dermatology, University of Luebeck, Luebeck, Germany.
authors.forename: Jennifer E
authors.initials: JE
authors.lastname: Kloepper
authors.affiliation: Institute of Inflammation and Repair, University of Manchester, Manchester, UK.|Department of Dermatology, University of Muenster, Muenster, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Paus
mesh_terms: D002460:Cell Line; D049109:Cell Proliferation; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D018859:Hair Follicle / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000473:pathology; D053583:Interleukin-1beta / Q000096:biosynthesis / Q000235:genetics; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics; D053569:Keratin-15 / Q000096:biosynthesis; D053539:Keratin-19 / Q000096:biosynthesis; D015603:Keratinocytes / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D058247:Loose Anagen Hair Syndrome / Q000235:genetics / Q000473:pathology*; D012333:RNA, Messenger / Q000096:biosynthesis; D017382:Reactive Oxygen Species / Q000378:metabolism; D013095:Spermidine / Q000031:analogs & derivatives* / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: C508585:IL1B protein, human; C508600:IL6 protein, human; D053583:Interleukin-1beta; D015850:Interleukin-6; C116015:KRT15 protein, human; D053569:Keratin-15; D053539:Keratin-19; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D007770:L-Lactate Dehydrogenase; D013095:Spermidine
keywords: Alopecia; Hair; Inflammation; Polyamines; Spermidine; TNF-alpha