p44/42 MAPK signaling is a prime target activated by phenylethyl resorcinol in its anti-melanogenic action
- Authors
- Kang, Mingyeong; Park, See-Hyoung; Park, Se Jung; Oh, Sae Woong; Yoo, Ju Ah; Kwon, Kitae; Kim, Jangsoon; Yu, Eunbi; Cho, Jae Youl; Lee, Jongsung
- Issue Date
- May-2019
- Publisher
- ELSEVIER GMBH
- Keywords
- Phenylethyl resorcinol; Melanogenesis; MITF; p44/42 MAPK; AP-1
- Citation
- PHYTOMEDICINE, v.58
- Journal Title
- PHYTOMEDICINE
- Volume
- 58
- URI
- https://scholarworks.bwise.kr/hongik/handle/2020.sw.hongik/1678
- DOI
- 10.1016/j.phymed.2019.152877
- ISSN
- 0944-7113
- Abstract
- Background: Melanin plays a crucial role in protecting human skin against exposure to ultraviolet (UV) radiation. However, its overproduction induces hyperpigmentation disorders of the skin. Purpose: To investigate effects of phenylethyl resorcinol as one resorcinol derivative on melanogenesis and its mechanisms using B16F10 mouse melanoma cells and human epidermal melanocytes. Methods: Effects of phenylethyl resorcinol on melanogenesis and its mechanism of action were examined using several in vitro assays (i.e., cell survival, melanin content, cellular tyrosinase activity, real-time PCR analysis, luciferase-reporter assay, Western blot analysis, and ELISAs for cyclic AMP (cAMP), protein kinase A (PKA), cAMP response element binding (CREB) protein, and mitogen-activated protein kinases (MAPKs)). Results: Phenylethyl resorcinol reduced both melanin content and tyrosinase activity in these cells. Phenylethyl resorcinol also suppressed tyrosinase activity in cell-free tyrosinase enzyme assay. Although phenylethyl resorcinol decreased mRNA levels of tyrosinase and tyrosinase-related protein (TRP)-2, it did not affect mRNA levels of melanogenic gene microphthalmia-associated transcriptional factor (MITF) or TRP-1. Phenylethyl resorcinol had no effects on cAMP signaling or NF-kappa B signaling based on results of cyclic AMP response element (CRE)-luciferase reporter assay, cAMP production, protein kinase A (PKA) activity, Western blot assays for phosphorylated CRE-binding protein (CREB), NF-kappa B-luciferase reporter assay, and Western blot assays for phosphorylated NF-kappa B. However, phenylethyl resorcinol induced activation of activator protein-1 (AP-1) signaling. Specifically, phenylethyl resorcinol increased AP-1 reporter activity and increased phosphorylation of p44/42 MAPK, but not p38 MAPK or c-Jun N-terminal kinase (JNK). MEK1/2 and Src, upstream molecules of p44/42 MAPK were also phosphorylated by phenylethyl resorcinol. In addition, phenylethyl resorcinol-induced decreases in melanin content, tyrosinase activity, and MITF protein levels were attenuated by PD98059, a p44/42 MAPK inhibitor. Conclusion: These data indicate that the anti-melanogenic activity of phenylethyl resorcinol is mediated by activation of p44/42 MAPK, indicating that phenylethyl resorcinol may be a potential therapeutic agent for treating hyperpigmentation skin disorders.
- Files in This Item
- There are no files associated with this item.
- Appears in
Collections - College of Science and Technology > Department of Biological and Chemical Engineering > 1. Journal Articles
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.