Rottlerin Reduces cAMP/CREB-Mediated Melanogenesis via Regulation of Autophagy

Qomaladewi, Nurinanda Prisky; Kim, Mi‐Yeon; Cho, Jae Youl

doi:10.3390/ijms20092081

Cited by 21 publications

(16 citation statements)

References 30 publications

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“…These results indicate that TSA regulates melanin secretion and intracellular melanin content in B16F10 cells by inhibiting the cAMP pathway. Tyrosinases are mediated in this process, and it is thought that the suppression of tyrosinase activity is an effective strategy for the suppression of melanin formation [ 1 , 36 ].…”

Section: Discussionmentioning

confidence: 99%

“…The skin is the largest tissue consisting of multiple epithelial tissues that protect muscles and organs, according to the definition of animal anatomy and dermatology [ 1 ]. The skin is a very important organization that protects the body from pathogens and maintains constancy [ 2 ] of insulation, body temperature control, sensory functions, the synthesis of vitamins, and the protection of vitamin B folate [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

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Antimelanogenesis Effects of Theasinensin A

Lim

Kim

Park

et al. 2021

IJMS

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Theasinensin A (TSA) is a major group of catechin dimers mainly found in oolong tea and black tea. This compound is also manufactured with epigallocatechin gallate (EGCG) as a substrate and is refined after the enzyme reaction. In previous studies, TSA has been reported to be effective against inflammation. However, the effect of these substances on skin melanin formation remains unknown. In this study, we unraveled the role of TSA in melanogenesis using mouse melanoma B16F10 cells and normal human epidermal melanocytes (NHEMs) through reverse transcription polymerase chain reaction (RT-PCR), Western blotting analysis, luciferase reporter assay, and enzyme-linked immunosorbent assay analysis. TSA inhibited melanin formation and secretion in α-melanocyte stimulating hormone (α-MSH)-induced B16F10 cells and NHEMs. TSA down-regulated the mRNA expression of tyrosinase (Tyr), tyrosinase-related protein 1 (Tyrp1), and Tyrp2, which are all related to melanin formation in these cells. TSA was able to suppress the activities of certain proteins in the melanocortin 1 receptor (MC1R) signaling pathway associated with melanin synthesis in B16F10 cells: cyclic adenosine monophosphate (cAMP) response element-binding protein (CREB), protein kinase A (PKA), tyrosinase, and microphthalmia-associated transcription factor (MITF). We also confirmed α-MSH-mediated CREB activities through a luciferase reporter assay, and that the quantities of cAMP were reduced by TSA in the enzyme linked immunosorbent assay (ELISA) results. Based on these findings, TSA should be considered an effective inhibitor of hyperpigmentation.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Antimelanogenesis Effects of Theasinensin A

Lim

Kim

Park

et al. 2021

IJMS

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“…Among the topranked endocrine system pathways, we distinguish the estrogen signaling pathway targeted by 131 activators, 25 inhibitors, and 14 dual-modulators; whereas melanogenesis is exclusively targeted by autophagy activators (see Supplementary Table S6). Recent studies show that rottlerin, an autophagy activator, regulates melanogenesis by targeting the cAMP-CREB signaling pathway [79].…”

Section: Functional Analysis Of the Targets Reveals Enriched Pathwaysmentioning

confidence: 99%

Mechanisms of Action of Autophagy Modulators Dissected by Quantitative Systems Pharmacology Analysis

Shi

Pei

Perlmutter

et al. 2020

Preprint

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Autophagy plays an essential role in cell survival/death and functioning. Modulation of autophagy has been recognized as a promising therapeutic strategy against diseases/disorders associated with uncontrolled growth or accumulation of biomolecular aggregates, organelles or cells including those caused by cancer, aging, neurodegeneration, and liver diseases such as α1antitrypsin deficiency. Numerous pharmacological agents that enhance or suppress autophagy have been discovered. However, their molecular mechanisms of action are far from clear. Here we collected a set of 225 autophagy modulators and carried out a comprehensive quantitative systems pharmacology (QSP) analysis of their targets using both existing databases and predictions made by our machine learning algorithm. Autophagy modulators include several highly promiscuous drugs (e.g. artenimol and olanzapine acting as activator, fostamatinib as inhibitor, or melatonin as dual-modulator), as well as selected drugs uniquely targeting specific proteins (~30% of modulators). They are mediated by three layers of regulation: (i) pathways involving core autophagy-related (ATG) proteins such as mTOR, AKT, and AMPK; (ii) upstream signaling events that regulates the activity of ATG pathways such as calcium-, cAMP-, and MAPK-signaling pathways; and (iii) transcription factors regulating the expression ATG proteins such as TFEB, TFE3, HIF-1, FoxO, and NF-κB. Our results suggest that PKA serves as a linker bridging between various signal transduction events and autophagy. These new insights contribute to a better assessment of the mechanism of action of autophagy modulators as well as their side effects, development of novel polypharmacological strategies, and identification of drug repurposing opportunities.

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“…Rottlerin, çeşitli hücre kültürleri üzerinde yapılan çalışmalarda bir otofaji aktivatörü olarak kullanılmıştır [12][13][14] . Chhiber ve ark.…”

Section: Introductionunclassified

Ratlarda Rottlerin’in Otofaji Üzerine Etkili Doz Düzeyinin Araştırılması

et al. 2021

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Otofaji, hücresel homeostazda rol oynayan fizyolojik bir süreçtir. Bununla birlikte, otofajik anomaliler kanser, nörodejeneratif hastalıklar ve kardiyovasküler hastalıklar gibi birçok patolojik durumla ilişkilidir. Rottlerin, otofajinin hastalıklarla ilişkisini değerlendirmek için kullanılabilecek ve tedavi stratejilerinde uygulanabilecek önemli bir otofaji aktivatörüdür. Ancak literatürde sıçanlarda otofajinin aktive edilmesinde bu molekülün dozları ile ilgili herhangi bir çalışma bulunmamaktadır. Bu çalışmanın amacı, Rottlerin'in sıçanlarda otofaji üzerindeki etkili doz düzeyinin araştırılmasıdır.Yöntemler: Yirmi dört rat, her biri altı rat içeren dört gruba ayrıldı. Grup I'e (kontrol grubu) Rottlerin'in çözücüsü (DMSO) verildi. Grup II, III ve IV'e, sırasıyla, 0,5, 2 ve 4 mg/kg Rottlerin intraperitoneal olarak uygulandı. Ratların kalp dokuları otofajik vakuol, LC3B seviyeleri ve anti-LC3B boyanma paterni açısından incelendi. Ayrıca, kan örneklerinde LC3B seviyeleri ölçüldü.Bulgular: Kalp dokularında otofajik vakuol, LC3B düzeyleri ve anti-LC3B boyanma paternleri açısından gruplar arasında anlamlı bir farklılık yoktu. Rottlerin dozu arttıkça, serum LC3B seviyelerinde artış eğilimi gözlendi; ancak, farklılıklar istatistiksel olarak anlamlı değildi.Sonuçlar: Sonuç olarak, bu çalışmanın bulgularına göre, ratlarda Rottlerin kullanılarak kalp dokusunda otofajiyi aktive etmek için mevcut dozların ve/veya uygulama süresinin artırılması gerektiği görülmektedir. Bununla birlikte, serum sonuçları, farklı dokularda otofajik aktivitenin artmış olabileceğini göstermektedir.

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Rottlerin Reduces cAMP/CREB-Mediated Melanogenesis via Regulation of Autophagy

Cited by 21 publications

References 30 publications

Antimelanogenesis Effects of Theasinensin A

Antimelanogenesis Effects of Theasinensin A

Mechanisms of Action of Autophagy Modulators Dissected by Quantitative Systems Pharmacology Analysis

Ratlarda Rottlerin’in Otofaji Üzerine Etkili Doz Düzeyinin Araştırılması

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