α-Viniferin Improves Facial Hyperpigmentation via Accelerating Feedback Termination of cAMP/PKA-Signaled Phosphorylation Circuit in Facultative Melanogenesis
| Autor: | Yong Pyo Choi, Bang Yeon Hwang, Jin Yong Song, Ju Yeon Kim, Youngsoo Kim, Jungno Lee, Seon Mi Ko, Cheong-Yong Yun, Song-Hee Kim, Jin Tae Hong, Sang-Bae Han, Beom Joon Kim, Jae Mun Kim |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
melanogenesis
Adult 0301 basic medicine Tyrosinase Immunoblotting Medicine (miscellaneous) Melanocyte Caragana sinica Real-Time Polymerase Chain Reaction CREB PKA inactivation Melanosis Melanin Young Adult 03 medical and health sciences Genes Reporter Cell Line Tumor Cyclic AMP medicine Humans Immunoprecipitation Phosphorylation Protein kinase A Pharmacology Toxicology and Pharmaceutics (miscellaneous) Benzofurans Feedback Physiological Melanins α-viniferin Korea biology Plant Extracts Chemistry Middle Aged biology.organism_classification Microphthalmia-associated transcription factor Cyclic AMP-Dependent Protein Kinases Caragana Cell biology Treatment Outcome 030104 developmental biology medicine.anatomical_structure Skin hyperpigmentation biology.protein Melanocytes Female feedback loop Research Paper |
| Zdroj: | Theranostics |
| ISSN: | 1838-7640 |
| Popis: | Rationale: cAMP up-regulates microphthalmia-associated transcription factor subtype M (MITF-M) and tyrosinase (Tyro) in the generation of heavily pigmented melanosomes. Here, we communicate a therapeutic mechanism of hyperpigmented disorder by α-viniferin, an active constituent of Caragana sinica. Methods: We used cAMP-elevated melanocyte cultures or facial hyperpigmented patches for pigmentation assays, and applied immunoprecipitation, immunobloting, RT-PCR or reporter gene for elucidation of the antimelanogenic mechanism. Results: C. sinica or α-viniferin inhibited melanin production in α-melanocyte-stimulating hormone (α-MSH)-, histamine- or cell-permeable cAMP-activated melanocyte cultures. Moreover, topical application with C. sinica containing α-viniferin, a standard in quality control, decreased melanin index on facial melasma and freckles in patients. As a molecular basis, α-viniferin accelerated protein kinase A (PKA) inactivation via the reassociation between catalytic and regulatory subunits in cAMP-elevated melanocytes, a feedback loop in the melanogenic process. α-Viniferin resultantly inhibited cAMP/PKA-signaled phosphorylation of cAMP-responsive element-binding protein (CREB) coupled with dephosphorylation of cAMP-regulated transcriptional co-activator 1 (CRTC1), thus down-regulating expression of MITF-M or Tyro gene with decreased melanin pigmentation. Conclusion: This study assigned PKA inactivation, a feedback termination in cAMP-induced facultative melanogenesis, as a putative target of α-viniferin in the treatment of melanocyte-specific hyperpigmented disorder. Finally, C. sinica containing α-viniferin was approved as an antimelanogenic agent with topical application in skin hyperpigmentation. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|