Schisandrin B inhibits α-melanocyte-stimulating hormone-induced melanogenesis in B16F10 cells via downregulation of MAPK and CREB signaling pathways

2020 ◽  
Vol 85 (4) ◽  
pp. 834-841
Author(s):  
Na Zhao ◽  
Xiaoming Su ◽  
He Li ◽  
Zhengyi Li ◽  
Yueyang Wang ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Camp Response Element Binding ◽  
Schisandrin B ◽  
Camp Response Element ◽  
Melanocyte Stimulating Hormone ◽  
B16f10 Cells ◽  
Kinase C ◽  
Element Binding Protein ◽  
Tyrosinase Related Protein ◽  
Stimulating Hormone

ABSTRACT Schisandrin B (Sch B), a lignan compound in Schisandra, possesses antioxidant, anti-inflammatory, and antiobesity activities. The effect of Sch B on melanogenesis and molecular mechanisms are still unknown. Therefore, we aimed to investigate the antimelanogenic effects of Sch B on α-melanocyte-stimulating hormone–induced B16F10 cells and elucidate the underlying molecular mechanisms. We found that Sch B significantly suppressed melanin content and mushroom tyrosinase (TYR) activity. Sch B treatment decreased the expression of TYR, melanocyte-inducing transcription factor (MITF), tyrosinase-related protein (TRP) 1, and TRP2. Moreover, Sch B modulated the phosphorylation of p38, extracellular-regulated protein kinase, c-Jun N-terminal kinase, and cAMP-response element binding protein (CREB), implying that these pathways may be involved in suppressing melanogenesis. Furthermore, we found that Sch B decreased melanogenesis by downregulating MITF and melanogenic enzymes via MAPK and CREB pathways. Overall, these findings indicate that Sch B has the potential use in whitening.

scholarly journals Protocatechuic Aldehyde Inhibits α-MSH-Induced Melanogenesis in B16F10 Melanoma Cells via PKA/CREB–Associated MITF Downregulation

2021 ◽  
Vol 22 (8) ◽  
pp. 3861
Author(s):  
Seok-Chun Ko ◽  
Seung-Hong Lee
Keyword(s):  
Molecular Mechanisms ◽  
3D Structure ◽  
Camp Response Element Binding ◽  
Melanoma Cells ◽  
Dependent Manner ◽  
Camp Response Element ◽  
B16f10 Cells ◽  
Protocatechuic Aldehyde ◽  
Element Binding Protein ◽  
Dependent Protein

Protocatechuic aldehyde (PA) is a naturally occurring phenolic compound that is a potent inhibitor of mushroom tyrosinase. However, the molecular mechanisms of the anti-melanogenesis activity of PA have not yet been reported. The aim of the current study was to clarify the melanogenesis inhibitory effects of PA and its molecular mechanisms in murine melanoma cells (B16F10). We first predicted the 3D structure of tyrosinase and used a molecular docking algorithm to simulate binding between tyrosinase and PA. These molecular modeling studies calculated a binding energy of −527.42 kcal/mol and indicated that PA interacts with Cu400 and 401, Val283, and His263. Furthermore, PA significantly decreased α-MSH-induced intracellular tyrosinase activity and melanin content in a dose-dependent manner. PA also inhibited key melanogenic proteins such as tyrosinase, tyrosinase-related protein 1 (TRP-1), and TRP-2 in α-MSH-stimulated B16F10 cells. In addition, PA decreased MITF expression levels by inhibiting phosphorylation of cAMP response element-binding protein (CREB) and cAMP-dependent protein kinase A (PKA). These results demonstrate that PA can effectively suppress melanin synthesis in melanoma cells. Taken together, our results show that PA could serve as a potential inhibitor of melanogenesis, and hence could be explored as a possible skin-lightening agent.

scholarly journals Extracts ofArtocarpus communisDecreaseα-Melanocyte Stimulating Hormone-Induced Melanogenesis through Activation of ERK and JNK Signaling Pathways

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Yi-Tzu Fu ◽  
Chiang-Wen Lee ◽  
Horng-Huey Ko ◽  
Feng-Lin Yen
Keyword(s):  
Skin Diseases ◽  
Folk Medicine ◽  
Camp Response Element Binding ◽  
Melanin Content ◽  
Agricultural Plant ◽  
Melanocyte Stimulating Hormone ◽  
B16f10 Cells ◽  
Extracellular Signal ◽  
Element Binding Protein ◽  
Stimulating Hormone

Artocarpus communisis an agricultural plant that is also used in folk medicine to prevent skin diseases, including acne and dermatitis. Extracts ofA. communishave been used to effectively inhibit melanogenesis; however, the antimelanogenesis mechanism of these extracts has not yet been investigated. The present study utilized a cell-free tyrosinase assay as well asα-melanocyte stimulating hormone- (-MSH-) induced tyrosinase assay conducted in B16F10 cells, performed a cytotoxicity assay, and determined cellular melanin content to examine the effects of a methanolic extract ofA. communis(ACM) and various organic partition fractions ofA. communison melanogenesis. In addition, we performed western blot analysis to elucidate the mechanism of their antimelanogenesis effect. Our results indicated that, except for the n-hexane extract, ACM and the various partition extracts at noncytotoxic concentrations effectively decreased melanin content and tyrosinase activity by downregulating microphthalmia-associated transcription factor (MITF) and phosphorylated cAMP response element-binding protein (p-CREB). Moreover, ACM and the partition fractions activated phosphorylation of extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) to inhibit the synthesis of MITF and finally to decrease melanin production. In conclusion, we suggest that noncytotoxic concentrations of ACM and the various partition fractions may be useful as references for developing skin-lighting agents for use in medicines or cosmetics.

scholarly journals 7,3′,4′-Trihydroxyisoflavone, a Metabolite of the Soy Isoflavone Daidzein, Suppresses α-Melanocyte-Stimulating Hormone-Induced Melanogenesis by Targeting Melanocortin 1 Receptor

2020 ◽  
Vol 7 ◽  
Author(s):  
Ji Hye Kim ◽  
Jae-Eun Lee ◽  
Taewon Kim ◽  
Myung Hun Yeom ◽  
Jun Seong Park ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Intracellular Camp ◽  
Related Protein ◽  
Melanin Production ◽  
Melanocortin 1 Receptor ◽  
Creb Phosphorylation ◽  
Melanocyte Stimulating Hormone ◽  
B16f10 Cells ◽  
Tyrosinase Related Protein ◽  
Stimulating Hormone

7,3′,4′-Trihydroxyisoflavone (7,3′,4′-THIF) is a metabolite of daidzein which is a representative isoflavone found in soybean. Recent studies suggested that 7,3′,4′-THIF exerts a hypopigmentary effect in B16F10 cells, however, its underlying molecular mechanisms and specific target protein remain unknown. Here, we found that 7,3′,4′-THIF, but not daidzein, inhibited α-melanocyte-stimulating hormone (MSH)-induced intracellular and extracellular melanin production in B16F10 cells by directly targeting melanocortin 1 receptor (MC1R). Western blot data showed that 7,3′,4′-THIF inhibited α-MSH-induced tyrosinase, tyrosinase-related protein-1 (TYRP-1), and tyrosinase-related protein-2 (TYRP-2) expressions through the inhibition of Microphthalmia-associated transcription factor (MITF) expression and cAMP response element-binding (CREB) phosphorylation. 7,3′,4′-THIF also inhibited α-MSH-induced dephosphorylation of AKT and phosphorylation of p38 and cAMP-dependent protein kinase (PKA). cAMP and Pull-down assays indicated that 7,3′,4′-THIF strongly inhibited forskolin-induced intracellular cAMP production and bound MC1R directly by competing with α-MSH. Moreover, 7,3′,4′-THIF inhibited α-MSH-induced intracellular melanin production in human epidermal melanocytes (HEMs). Collectively, these results demonstrate that 7,3′,4′-THIF targets MC1R, resulting in the suppression of melanin production, suggesting a protective role for 7,3′,4′-THIF against melanogenesis.

scholarly journals CREB mediates the C. elegans dauer polyphenism through direct and cell-autonomous regulation of TGF-β expression

PLoS Genetics ◽  
2021 ◽  
Vol 17 (7) ◽  
pp. e1009678
Author(s):  
JiSoo Park ◽  
Hyekyoung Oh ◽  
Do-Young Kim ◽  
YongJin Cheon ◽  
Yeon-Ji Park ◽  
...  
Keyword(s):  
Developmental Plasticity ◽  
Molecular Mechanisms ◽  
Environmental Changes ◽  
Marker Gene ◽  
Camp Response Element Binding ◽  
Camp Response Element ◽  
Developmental Programs ◽  
C Elegans ◽  
Element Binding Protein

Animals can adapt to dynamic environmental conditions by modulating their developmental programs. Understanding the genetic architecture and molecular mechanisms underlying developmental plasticity in response to changing environments is an important and emerging area of research. Here, we show a novel role of cAMP response element binding protein (CREB)-encoding crh-1 gene in developmental polyphenism of C. elegans. Under conditions that promote normal development in wild-type animals, crh-1 mutants inappropriately form transient pre-dauer (L2d) larva and express the L2d marker gene. L2d formation in crh-1 mutants is specifically induced by the ascaroside pheromone ascr#5 (asc-ωC3; C3), and crh-1 functions autonomously in the ascr#5-sensing ASI neurons to inhibit L2d formation. Moreover, we find that CRH-1 directly binds upstream of the daf-7 TGF-β locus and promotes its expression in the ASI neurons. Taken together, these results provide new insight into how animals alter their developmental programs in response to environmental changes.

scholarly journals Prefrontal Cortex in Learning to Overcome Generalized Fear

2015 ◽  
Vol 9 ◽  
pp. JEN.S26227 ◽  
Author(s):  
Edward Korzus
Keyword(s):  
Prefrontal Cortex ◽  
Discrimination Learning ◽  
Molecular Mechanisms ◽  
Critical Role ◽  
Camp Response Element Binding ◽  
Normal Brain ◽  
Camp Response Element ◽  
Brain Functioning ◽  
Element Binding Protein

Normal brain functioning relies critically on the ability to control appropriate behavioral responses to fearful stimuli. Overgeneralized fear is the major symptom of anxiety disorders including posttraumatic stress disorder. This review describes recent data demonstrating that the medial prefrontal cortex (mPFC) plays a critical role in the refining of cues that drive the acquisition of fear response. Recent studies on molecular mechanisms that underlie the role of mPFC in fear discrimination learning are discussed. These studies suggest that prefrontal N-methyl-D-aspartate receptors expressed in excitatory neurons govern fear discrimination learning via a mechanism involving cAMP response element-binding protein-dependent engagement of acetyltransferase.

scholarly journals A novel pathway for adrenergic stimulation of cAMP-response-element-binding protein (CREB) phosphorylation: mediation via α1-adrenoceptors and protein kinase C activation

2002 ◽  
Vol 364 (1) ◽  
pp. 73-79 ◽  
Author(s):  
Håkan THONBERG ◽  
J. Magnus FREDRIKSSON ◽  
Jan NEDERGAARD ◽  
Barbara CANNON
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Camp Response Element Binding ◽  
Camp Response Element ◽  
Response Element ◽  
Creb Phosphorylation ◽  
Kinase C ◽  
Adrenergic Antagonist ◽  
Element Binding Protein ◽  
Protein Kinase C Activation

Because of the central role of adrenergic mechanisms in the expression of crucial genes during brown adipocyte differentiation, we examined the activation (phosphorylation) of CREB (cAMP-response-element-binding protein) in mouse brown adipocytes in primary culture. We found that noradrenaline (‘norepinephrine’) stimulated CREB phosphorylation rapidly (maximum effect in ≤ 5min with slow decay) and efficiently (EC50, 6nM). The increase in CREB phosphorylation coincided with increased expression of an artificial cAMP-response-element-containing reporter construct. CREB phosphorylation was partly inhibitable, both by the β-adrenergic antagonist propranolol and by the α1-adrenergic antagonist prazosin. Adenylate cyclase hyperactivation (by forskolin) could stimulate CREB phosphorylation to the same extent as noradrenaline. The α1-adrenergic agonist cirazoline also increased CREB phosphorylation. An increase in intracellular [Ca2+] had, however, no effect, but protein kinase C activation by PMA was a potent stimulator. The cirazoline-stimulated (α1-adrenergic) CREB phosphorylation was inhibited by a desensitizing pretreatment with PMA, demonstrating that the α1-stimulation was mediated via protein kinase C activation; neither Src nor extracellular-signal-regulated kinases 1 and 2 activation was involved in the signalling process. We conclude that CREB phosphorylation in brown adipocytes is mediated not only through the classical β-adrenergic/cAMP pathway but also through a novel α1-adrenergic/protein kinase C/CREB pathway, which has not been described previously in any tissue.

scholarly journals GADD45β Regulates Hepatic Gluconeogenesis via Modulating the Protein Stability of FoxO1

Biomedicines ◽  
2021 ◽  
Vol 9 (1) ◽  
pp. 50
Author(s):  
Hyunmi Kim ◽  
Da Som Lee ◽  
Tae Hyeon An ◽  
Tae-Jun Park ◽  
Eun-Woo Lee ◽  
...  
Keyword(s):  
Protein Stability ◽  
Molecular Mechanisms ◽  
Camp Response Element Binding ◽  
Whole Body ◽  
Camp Response Element ◽  
Hepatic Gluconeogenesis ◽  
Creb Phosphorylation ◽  
Glucose Levels ◽  
Element Binding Protein ◽  
Glucose Output

Increased hepatic gluconeogenesis is one of the main contributors to the development of type 2 diabetes. Recently, it has been reported that growth arrest and DNA damage-inducible 45 beta (GADD45β) is induced under both fasting and high-fat diet (HFD) conditions that stimulate hepatic gluconeogenesis. Here, this study aimed to establish the molecular mechanisms underlying the novel role of GADD45β in hepatic gluconeogenesis. Both whole-body knockout (KO) mice and adenovirus-mediated knockdown (KD) mice of GADD45β exhibited decreased hepatic gluconeogenic gene expression concomitant with reduced blood glucose levels under fasting and HFD conditions, but showed a more pronounced effect in GADD45β KD mice. Further, in primary hepatocytes, GADD45β KD reduced glucose output, whereas GADD45β overexpression increased it. Mechanistically, GADD45β did not affect Akt-mediated forkhead box protein O1 (FoxO1) phosphorylation and forskolin-induced cAMP response element-binding protein (CREB) phosphorylation. Rather it increased FoxO1 transcriptional activity via enhanced protein stability of FoxO1. Further, GADD45β colocalized and physically interacted with FoxO1. Additionally, GADD45β deficiency potentiated insulin-mediated suppression of hepatic gluconeogenic genes, and it were impeded by the restoration of GADD45β expression. Our finding demonstrates GADD45β as a novel and essential regulator of hepatic gluconeogenesis. It will provide a deeper understanding of the FoxO1-mediated gluconeogenesis.

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