Topical Application of a Protein Kinase C Inhibitor Reduces Skin and Hair Pigmentation
| Autor: | Jin Lee, Salvador González, Hee-Young Park, Maritza A. Middelkamp-Hup, Barbara A. Gilchrest, Sameer Kapasi, Shaun E. Peterson |
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| Přispěvatelé: | Amsterdam institute for Infection and Immunity, Dermatology |
| Rok vydání: | 2004 |
| Předmět: |
PKC-beta
Bisindolylmaleimide Indoles Ultraviolet Rays Tyrosinase Guinea Pigs PKC inhibitor Dermatology In Vitro Techniques Pharmacology Biology Biochemistry Maleimides Melanin Mice chemistry.chemical_compound In vivo Protein Kinase C beta Animals Humans Enzyme Inhibitors Hair Color Protein kinase A Molecular Biology Cells Cultured Protein Kinase C Protein kinase C Melanins Microscopy Confocal integumentary system Epidermis (botany) Monophenol Monooxygenase Kinase hair Cell Biology Mice Inbred C57BL Epidermal Cells chemistry Melanocytes Female skin pigmentation |
| Zdroj: | Journal of investigative dermatology, 122(1), 159-166. Nature Publishing Group |
| ISSN: | 0022-202X |
| Popis: | To determine whether inhibition of PKC-beta activity decreases pigmentation, paired cultures of primary human melanocytes were first pretreated with bisindolylmaleimide (Bis), a selective PKC inhibitor, or vehicle alone for 30 min, and then treated with TPA for an additional 90 min to activate PKC in the presence of Bis. Bis blocked the expected induction of tyrosinase activity by activation of PKC. Addition of a peptide corresponding to amino acids 501-511 of tyrosinase containing its PKC-beta phosphorylation site, a presumptive PKC-beta pseudosubstrate, gave similar results. To determine whether Bis reduces pigmentation in vivo, the backs of four shaved and depilated pigmented guinea pigs were UV irradiated with a solar simulator for 2 wk excluding weekends. Compared to vehicle alone, Bis (300 microM), applied twice daily to paired sites for various periods encompassing the irradiation period, decreased tanning. Bis also, although less strikingly, reduced basal epidermal melanin when topically applied twice daily, 5 d per wk, for 3 wk to shaved and depilated unirradiated skin. Moreover, topical application of Bis (100 microM) once daily for 9 d to the freshly depilated backs of 8-wk-old mice markedly lightened the color of regrowing hair. These results demonstrate that inhibiting PKC activity in vivo selectively blocks tanning and reduces basal pigmentation in the epidermis and in anagen hair shafts. |
| Databáze: | OpenAIRE |
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