scholarly journals Jeju Magma-Seawater Inhibits α-MSH-Induced Melanogenesis via CaMKKβ-AMPK Signaling Pathways in B16F10 Melanoma Cells

Marine Drugs ◽  
2020 ◽  
Vol 18 (9) ◽  
pp. 473
Author(s):  
Minhyeok Song ◽  
Jihyun Lee ◽  
Young-Joo Kim ◽  
Dang Hieu Hoang ◽  
Wonchae Choe ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Signaling Pathways ◽  
Skin Pigmentation ◽  
Adenosine Monophosphate ◽  
Melanoma Cells ◽  
Mitogen Activated Protein Kinase ◽  
B16f10 Melanoma ◽  
Ampk Signaling ◽  
Calcium Calmodulin Dependent ◽  
B16f10 Melanoma Cells

Melanin protects skin from ultraviolet radiation, toxic drugs, and chemicals. Its synthesis is sophisticatedly regulated by multiple mechanisms, including transcriptional and enzymatic controls. However, uncontrolled excessive production of melanin can cause serious dermatological disorders, such as freckles, melasma, solar lentigo, and cancer. Moreover, melanogenesis disorders are also linked to neurodegenerative diseases. Therefore, there is a huge demand for safer and more potent inhibitors of melanogenesis. In the present study, we report novel inhibitory effects of Jeju magma-seawater (JMS) on melanogenesis induced by α-melanocyte stimulating hormone (α-MSH) in B16F10 melanoma cells. JMS is the abundant underground seawater found in Jeju Island, a volcanic island of Korea. Research into the physiological effects of JMS is rapidly increasing due to its high contents of various minerals that are essential to human health. However, little is known about the effects of JMS on melanogenesis. Here, we demonstrate that JMS safely and effectively inhibits α-MSH-induced melanogenesis via the CaMKKβ (calcium/calmodulin-dependent protein kinase β)-AMPK (5′ adenosine monophosphate-activated protein kinase) signaling pathway. We further demonstrate that AMPK inhibits the signaling pathways of protein kinase A and MAPKs (mitogen-activated protein kinase), which are critical for melanogenesis-related gene expression. Our results highlight the potential of JMS as a novel therapeutic agent for ameliorating skin pigmentation-related disorders.

scholarly journals Melanogenic Effects of Maclurin Are Mediated through the Activation of cAMP/PKA/CREB and p38 MAPK/CREB Signaling Pathways

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Young Sun Hwang ◽  
Sae Woong Oh ◽  
See-Hyoung Park ◽  
Jienny Lee ◽  
Ju Ah. Yoo ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Signaling Pathways ◽  
P38 Mapk ◽  
Adenosine Monophosphate ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Protective Agent ◽  
Protective Effects ◽  
Skin Disorders ◽  
Creb Phosphorylation

Melanogenesis is the biological process which the skin pigment melanin is synthesized to protect the skin against ultraviolet irradiation and other external stresses. Abnormal biology of melanocytes is closely associated with depigmented skin disorders such as vitiligo. In this study, we examined the effects of maclurin on melanogenesis and cytoprotection. Maclurin enhanced cellular tyrosinase activity as well as cellular melanin levels. We found that maclurin treatment increased the expression of microphthalmia-associated transcription factor (MITF), tyrosinase-related protein- (TRP-) 1, TRP-2, and tyrosinase. Mechanistically, maclurin promoted melanogenesis through cyclic adenosine monophosphate (cAMP) response element binding (CREB) protein-dependent upregulation of MITF. CREB activation was found to be mediated by p38 mitogen-activated protein kinase (MAPK) or cAMP-protein kinase A (PKA) signaling. In addition, maclurin-induced CREB phosphorylation was mediated through the activation of both the cAMP/PKA and the p38 MAPK signaling pathways. Maclurin-induced suppression of p44/42 MAPK activation also contributed to its melanogenic activity. Furthermore, maclurin showed protective effects against H2O2 treatment and UVB irradiation in human melanocytes. These findings indicate that the melanogenic effects of maclurin depend on increased MITF gene expression, which is mediated by the activation of both p38 MAPK/CREB and cAMP/PKA/CREB signaling. Our results thus suggest that maclurin could be useful as a protective agent against hypopigmented skin disorders.

scholarly journals Metabolomics Reveals the Alteration of Metabolic Pathway by Alpha-Melanocyte-Stimulating Hormone in B16F10 Melanoma Cells

Molecules ◽  
2020 ◽  
Vol 25 (15) ◽  
pp. 3384 ◽  
Author(s):  
Seung-Ho Seo ◽  
Jae Kwon Jo ◽  
Eun-Ju Kim ◽  
Seong-Eun Park ◽  
Seo Yeon Shin ◽  
...  
Keyword(s):  
Citric Acid ◽  
Metabolic Pathway ◽  
Metabolic Pathways ◽  
Skin Pigmentation ◽  
Principal Component ◽  
Melanoma Cells ◽  
B16f10 Melanoma ◽  
Melanocyte Stimulating Hormone ◽  
B16f10 Melanoma Cells ◽  
Stimulating Hormone

The purpose of this study was to understand the changes of metabolic pathway induced by alpha-melanocyte-stimulating hormone (α-MSH) in B16F10 melanoma cells in an untargeted metabolomics approach. Cells were treated with 100 nM of α-MSH and then incubated for 48 h. α-MSH increased tyrosinase activity and melanin content by 56.5 and 61.7%, respectively, compared to untreated cells after 48 h of cultivation. The clear separation between groups was observed in the principal component analysis score plot, indicating that the levels of metabolites of melanoma cells were altered by treatment with α-MSH. Metabolic pathways affected by α-MSH were involved in some amino acid metabolisms. The increased levels of fumaric acid, malic acid, oxaloacetic acid and citric acid related to the citric acid cycle pathway after α-MSH treatment suggested enhanced energy metabolism. Metabolic pathways altered by α-MSH treatment can provide useful information to develop new skin pigmentation inhibitors or anti-obesity drugs.

scholarly journals p38 Mitogen-activated Protein Kinase-, Calcium-Calmodulin–dependent Protein Kinase-, and Calcineurin-mediated Signaling Pathways Transcriptionally Regulate Myogenin Expression

2002 ◽  
Vol 13 (6) ◽  
pp. 1940-1952 ◽  
Author(s):  
Qing Xu ◽  
Lu Yu ◽  
Lanying Liu ◽  
Ching Fung Cheung ◽  
Xue Li ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Signaling Pathways ◽  
Histone Deacetylases ◽  
Mitogen Activated Protein Kinase ◽  
Cis Elements ◽  
Dependent Protein Kinase ◽  
Calcium Calmodulin Dependent ◽  
Mitogen Activated Protein ◽  
Rd Cells ◽  
Dependent Protein

In this report, we identify myogenin as an important transcriptional target under the control of three intracellular signaling pathways, namely, the p38 mitogen-activated protein kinase- (MAPK), calcium-calmodulin–dependent protein kinase- (CaMK), and calcineurin-mediated pathways, during skeletal muscle differentiation. Three cis-elements (i.e., the E box, myocyte enhancer factor [MEF] 2, and MEF3 sites) in the proximal myogenin promoter in response to these three pathways are defined. MyoD, MEF2s, and Six proteins, the trans-activators bound to these cis-elements, are shown to be activated by these signaling pathways. Our data support a model in which all three signaling pathways act in parallel but nonredundantly to control myogenin expression. Inhibition of any one pathway will result in abolished or reduced myogenin expression and subsequent phenotypic differentiation. In addition, we demonstrate that CaMK and calcineurin fail to activate MEF2s in Rhabdomyosarcoma-derived RD cells. For CaMK, we show its activation in response to differentiation signals and its effect on the cytoplasmic translocation of histone deacetylases 5 are not compromised in RD cells, suggesting histone deacetylases 5 cytoplasmic translocation is necessary but not sufficient, and additional signal is required in conjunction with CaMK to activate MEF2 proteins.

scholarly journals Ethanolic Extract of Hippocampus abdominalis Exerts Anti-Melanogenic Effects in B16F10 Melanoma Cells and Zebrafish Larvae by Activating the ERK Signaling Pathway

Cosmetics ◽  
2019 ◽  
Vol 7 (1) ◽  
pp. 1 ◽  
Author(s):  
Ilandarage Menu Neelaka Molagoda ◽  
Yung Hyun Choi ◽  
Seungheon Lee ◽  
Jiwon Sung ◽  
Cho Rong Lee ◽  
...  
Keyword(s):  
Heart Rate ◽  
Signaling Pathway ◽  
Ethanolic Extract ◽  
Adenosine Monophosphate ◽  
Melanoma Cells ◽  
Erk Signaling ◽  
B16f10 Melanoma ◽  
Zebrafish Larvae ◽  
B16f10 Melanoma Cells ◽  
Hippocampus Abdominalis

The big belly seahorse (Hippocampus abdominalis), a well-known ingredient of traditional medicine, possesses anti-inflammatory, anti-aging, anti-fatigue, and anti-thrombotic properties, and also increases male fertility. This study demonstrates that the ethanolic extract of dried H. abdominalis (EEHA) has anti-melanogenic effects in B16F10 melanoma cells and zebrafish larvae. EEHA significantly reduced the α-melanocyte-stimulating hormone (α-MSH)-induced melanogenesis in B16F10 melanoma cells without causing cytotoxicity. At a concentration of 200 µg/mL, EEHA had significant anti-melanogenic activity in zebrafish larvae, accompanied by a severe reduction in the heart rate (118 ± 17 heartbeats/min) compared to that of the untreated group (185 ± 8 heartbeats/min), indicating that EEHA induces cardiotoxicity at high concentrations. Below 100 µg/mL, EEHA significantly reduced melanogenesis in zebrafish larvae in the presence or absence of α-MSH, while the heart rate remained unaltered. Additionally, EEHA downregulated the release of cyclic adenosine monophosphate (cAMP) and the phosphorylation of cAMP response element-binding protein (CREB) in B16F10 melanoma cells, which inhibited microphthalmia-associated transcription factor (MITF), leading to the inhibition of tyrosinase activity. EEHA also increased the phosphorylation of extracellular-signal regulated kinase (ERK). The ERK inhibitor PD98059 interfered with the anti-melanogenic activity of EEHA in B16F10 melanoma cells and zebrafish larvae, indicating that the ERK signaling pathway might regulate the anti-melanogenic properties of EEHA. Altogether, we conclude that EEHA represses the cAMP–CREB–MITF axis, which consequently inhibits tyrosinase-mediated melanogenesis. We propose that at low concentrations, EEHA can serve as a promising anti-melanogenic agent that could be used to prepare whitening cosmetics and for treating melanogenic disorders.

scholarly journals Inhibition of Calcium/Calmodulin-dependent Protein Kinase Kinase by Protein 14-3-3

2004 ◽  
Vol 279 (50) ◽  
pp. 52191-52199 ◽  
Author(s):  
Monika A. Davare ◽  
Takeo Saneyoshi ◽  
Eric S. Guire ◽  
Sean C. Nygaard ◽  
Thomas R. Soderling
Keyword(s):  
Protein Kinase ◽  
Signaling Pathways ◽  
Hippocampal Slices ◽  
Phosphorylation Site ◽  
Site Directed Mutagenesis ◽  
Mitogen Activated Protein Kinase ◽  
Calcium Signal ◽  
Dependent Protein Kinase ◽  
Calcium Calmodulin Dependent ◽  
Dependent Protein

Intracellular calcium concentrations regulate diverse cellular events including cytoskeletal dynamics, gene transcription, and synaptic plasticity. The calcium signal is transduced in part by the calcium/calmodulin-dependent protein kinase (CaMK) cascade that is comprised of CaMK kinase (CaMKK) and its primary downstream substrates, CaMKI and CaMKIV. The CaMK cascade also participates in cross-talk with other signaling pathways: CaMKK/CaMKI can activate the mitogen-activated protein kinase pathway and cAMP-dependent protein kinase (PKA) can directly phosphorylate two inhibitory sites (Thr108and Ser458) in CaMKK. Here we report an additional PKA-dependent regulation of CaMKK through its interaction with protein 14-3-3. CaMKK and 14-3-3 co-immunoprecipitated from co-transfected heterologous cells as well as from rat brain homogenate, and site-directed mutagenesis studies identified phospho-Ser74in CaMKK as the primary 14-3-3 binding site. In cultured rat hippocampal neurons and acute hippocampal slices this interaction was robustly stimulated by activation of PKA through forskolin treatment and was blocked by inhibition of PKA. Interaction of 14-3-3 with CaMKK had two regulatory consequencesin vitro. It directly inhibited CaMKK activity, and it also blocked dephosphorylation of Thr108, an inhibitory PKA phosphorylation site. In human embryonic kidney 293 cells transfected with CaMKK and stimulated with forskolin, co-transfection with 14-3-3 prevented dephosphorylation of Thr108to the same extent as did inhibition of protein phosphatases with okadaic acid. We conclude that binding of 14-3-3 to CaMKK stabilizes its inhibition by PKA-mediated phosphorylation, which may have important consequences in the regulation of CaMKI, CaMKIV, protein kinase B, and ERK signaling pathways.

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