دورية أكاديمية
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Targeting phosphorylation circuits on CREB and CRTCs as the strategy to prevent acquired skin hyperpigmentation.

التفاصيل البيبلوغرافية
العنوان: Targeting phosphorylation circuits on CREB and CRTCs as the strategy to prevent acquired skin hyperpigmentation.
المؤلفون: Kim SH; College of Pharmacy, Chungbuk National University, Cheongju 28160, Korea., Na C; College of Pharmacy, Chungbuk National University, Cheongju 28160, Korea., Yun CY; College of Pharmacy, Chungbuk National University, Cheongju 28160, Korea.; R&D Center, The Skin's Co. Ltd, Jecheon 27116, Korea., Kim JG; College of Pharmacy, Chungbuk National University, Cheongju 28160, Korea., Baek ST; R&D Center, The Skin's Co. Ltd, Jecheon 27116, Korea., An HJ; R&D Center, Yeomyung Biochem Co. Ltd, Cheongju 28172, Korea., Lee JD; R&D Center, Yeomyung Biochem Co. Ltd, Cheongju 28172, Korea., Lee SW; College of Pharmacy, Chungbuk National University, Cheongju 28160, Korea., Jung JK; College of Pharmacy, Chungbuk National University, Cheongju 28160, Korea., Hwang BY; College of Pharmacy, Chungbuk National University, Cheongju 28160, Korea., Han SB; College of Pharmacy, Chungbuk National University, Cheongju 28160, Korea., Kim Y; College of Pharmacy, Chungbuk National University, Cheongju 28160, Korea.
المصدر: International journal of biological sciences [Int J Biol Sci] 2024 Jan 01; Vol. 20 (1), pp. 312-330. Date of Electronic Publication: 2024 Jan 01 (Print Publication: 2024).
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Ivyspring International Country of Publication: Australia NLM ID: 101235568 Publication Model: eCollection Cited Medium: Internet ISSN: 1449-2288 (Electronic) Linking ISSN: 14492288 NLM ISO Abbreviation: Int J Biol Sci Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Lake Haven, N.S.W., Australia : Ivyspring International, c2004-
مواضيع طبية MeSH: Melanins*/metabolism , Hyperpigmentation*/metabolism, Humans ; Animals ; Mice ; Cyclic AMP Response Element-Binding Protein/metabolism ; Phosphorylation ; alpha-MSH/metabolism ; AMP-Activated Protein Kinases/metabolism ; Melanocytes/metabolism ; Microphthalmia-Associated Transcription Factor/genetics ; Microphthalmia-Associated Transcription Factor/metabolism ; Cell Line, Tumor
مستخلص: Background: The cAMP response element-binding protein (CREB) and CREB-regulated transcription coactivators (CRTCs) cooperate in the transcriptional activation of microphthalmia-associated transcription factor subtype M (MITF-M) that is a master regulator in the biogenesis, pigmentation and transfer of melanosomes at epidermal melanocytes. Here, we propose the targeting of phosphorylation circuits on CREB and CRTCs in the expression of MITF-M as the rationale to prevent skin hyperpigmentation by elucidating the inhibitory activity and mechanism of yakuchinone A (Yaku A) on facultative melanogenesis. Methods: We employed human epidermal melanocyte cell, mouse skin, and mouse melanoma cell, and applied Western blotting, reverse transcription-polymerase chain reaction, immunoprecipitation and confocal microscopy to conduct this study. Results: This study suggested that α-melanocyte stimulating hormone (α-MSH)-induced melanogenic programs could switch on the axis of protein kinase A-salt inducible kinases (PKA-SIKs) rather than that of PKA-AMP activated protein kinase (PKA-AMPK) during the dephosphorylation of CRTCs in the expression of MITF-M. SIK inhibitors rather than AMPK inhibitors stimulated melanin production in melanocyte cultures in the absence of extracellular melanogenic stimuli, wherein SIK inhibitors increased the dephosphorylation of CRTCs but bypassed the phosphorylation of CREB for the expression of MITF-M. Treatment with Yaku A prevented ultraviolet B (UV-B)-irradiated skin hyperpigmentation in mice and inhibited melanin production in α-MSH- or SIK inhibitor-activated melanocyte cultures. Mechanistically, Yaku A suppressed the expression of MITF-M via dually targeting the i) cAMP-dependent dissociation of PKA holoenzyme at the upstream from PKA-catalyzed phosphorylation of CREB coupled with PKA-SIKs axis-mediated dephosphorylation of CRTCs in α-MSH-induced melanogenic programs, and ii) nuclear import of CRTCs after SIK inhibitor-induced dephosphorylation of CRTCs. Conclusions: Taken together, the targeting phosphorylation circuits on CREB and CRTCs in the expression of MITF-M could be a suitable strategy to prevent pigmentary disorders in the skin.
Competing Interests: Competing Interests: The authors have declared that no competing interest exists.
(© The author(s).)
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فهرسة مساهمة: Keywords: Melanogenesis; SIK inhibitor; UV-B; Yaku A; α-MSH
المشرفين على المادة: 0 (Melanins)
0 (Cyclic AMP Response Element-Binding Protein)
581-05-5 (alpha-MSH)
EC 2.7.11.31 (AMP-Activated Protein Kinases)
0 (Microphthalmia-Associated Transcription Factor)
تواريخ الأحداث: Date Created: 20240102 Date Completed: 20240103 Latest Revision: 20240306
رمز التحديث: 20240306
مُعرف محوري في PubMed: PMC10750286
DOI: 10.7150/ijbs.86536
PMID: 38164184
قاعدة البيانات: MEDLINE
الوصف
تدمد:1449-2288
DOI:10.7150/ijbs.86536