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Published on: July 6, 2019
p44/42 MAPK signaling is a prime target activated by phenylethyl resorcinol in its anti-melanogenic action
Mingyeong Kang1, See-Hyoung Park2, Se Jung Park1
1Molecular Dermatology Laboratory, Department of Integrative Biotechnology, College of Biotechnology and Bioengineering, Sungkyunkwan University, Suwon City, 16419 Gyunggi Do, Republic of Korea.
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-κB 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-κB-luciferase reporter assay, and Western blot assays for phosphorylated NF-κB. 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.
Insights
Phenylethyl resorcinol effectively reduces skin melanin production by inhibiting tyrosinase activity and impacting MAPK signaling pathways. This suggests its potential as a therapeutic for hyperpigmentation disorders.
Area of Science:
- Dermatology and Molecular Biology
- Skin Physiology and Pigmentation
Background:
- Melanin protects skin from UV radiation but its overproduction causes hyperpigmentation.
- Understanding melanogenesis is key to treating skin pigmentation disorders.
Purpose of the Study:
- To investigate the effects of phenylethyl resorcinol on melanogenesis.
- To elucidate the underlying molecular mechanisms of phenylethyl resorcinol's action in B16F10 melanoma cells and human melanocytes.
Main Methods:
- In vitro assays including cell survival, melanin content, and tyrosinase activity measurements.
- Molecular analyses using real-time PCR, Western blot, luciferase reporter assays, and ELISAs.
- Investigated signaling pathways such as cAMP, NF-κB, and MAPKs (mitogen-activated protein kinases).
Main Results:
- Phenylethyl resorcinol decreased melanin content and tyrosinase activity in cells and in cell-free assays.
- It suppressed mRNA levels of tyrosinase and TRP-2 but not MITF or TRP-1.
- The compound activated activator protein-1 (AP-1) signaling via p44/42 MAPK phosphorylation, independent of cAMP and NF-κB pathways.
Conclusions:
- Phenylethyl resorcinol's anti-melanogenic activity is mediated by p44/42 MAPK activation.
- Its mechanism involves inhibiting key melanogenic enzymes and regulating transcription factors.
- Phenylethyl resorcinol shows promise as a therapeutic agent for hyperpigmentation disorders.
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