Cyclic adenosine monophosphate response-element binding protein activation by mitogen-activated protein kinase-activated protein kinase 3 and four-and-a-half LIM domains 5 plays a key role for vein graft intimal hyperplasia

The biosynthesis pathway of melanin is a series of oxidative reactions that are catalyzed by melanin-related proteins, including tyrosinase (TYR), tyrosinase-related protein-1 (TRP-1), and tyrosinase-related protein-2 (TRP-2). Reagents or materials with antioxidative or free radical-scavenging activities may be candidates for anti-melanogenesis. 3,4-Dihydroxybenzalacetone (DBL) is a polyphenol isolated from fungi, such as Phellinus obliguus (Persoon) Pilat and P. linteus. In this study, we investigated the effects and mechanisms of DBL on antioxidation and melanogenesis in murine melanoma cells (B16F10) and human epidermal melanocytes (HEMs). The results indicated that DBL scavenged 2,2-diphenyl-1-picrylhydrazyl (DPPH) and hydroxyl radicals, and exhibited potent reducing power, indicating that it displays strong antioxidative activity. DBL also inhibited the expression of TYR, TRP-1, TRP-2, and microphthalmia-related transcription factor (MITF) in both the cells. In addition, DBL inhibited hyperpigmentation in B16F10 and HEMs by regulating the cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA), v-akt murine thymoma viral oncogene homolog (AKT)/glycogen synthase kinase 3 beta (GSK3β), and mitogen-activated protein kinase kinase (MEK)/extracellular regulated protein kinase (ERK) signaling pathways. DBL not only shortened dendritic melanocytes but also inhibited premelanosome protein 17 (PMEL17) expression, slowing down the maturation of melanosome transportation. These results indicated that DBL promotes anti-melanogenesis by inhibiting the transportation of melanosomes. Therefore, DBL is a potent antioxidant and depigmenting agent that may be used in whitening cosmetics.

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A yeast MAPK cascade regulates pexophagy but not other autophagy pathways

The Journal of Cell Biology ◽

10.1083/jcb.200909154 ◽

2010 ◽

Vol 189 (2) ◽

pp. 303-310 ◽

Cited By ~ 50

Author(s):

Ravi Manjithaya ◽

Shveta Jain ◽

Jean-Claude Farré ◽

Suresh Subramani

Keyword(s):

Protein Kinase ◽

Mapk Pathway ◽

Signal Transduction Pathway ◽

Cyclic Adenosine Monophosphate ◽

Adenosine Monophosphate ◽

Mapk Cascade ◽

Mitogen Activated Protein Kinase ◽

Mitogen Activated Protein ◽

Simultaneous Activation ◽

Cellular Components

Autophagy is important for many cellular processes such as innate immunity, neurodegeneration, aging, and cancer. Although the signaling events triggering autophagy have been studied, little is known regarding the signaling mechanisms by which autophagy is redirected to achieve selective removal of cellular components. We have used the degradation of a peroxisomal marker to investigate the role of protein kinases in selective autophagy of peroxisomes (pexophagy) in Saccharomyces cerevisiae. We show that the Slt2p mitogen-activated protein kinase (MAPK) and several upstream components of its signal transduction pathway are necessary for pexophagy but not for pexophagosome formation or other nonselective and selective forms of autophagy. Other extracellular signals that activate this pathway do not trigger pexophagy on their own, suggesting that this MAPK cascade is necessary but not sufficient to trigger pexophagy. We propose that pexophagy requires the simultaneous activation of this MAPK pathway and a hexose-sensing mechanism acting through protein kinase A and cyclic adenosine monophosphate.

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Cooperative Effects between Protein Kinase A and p44/p42 Mitogen-Activated Protein Kinase to Promote cAMP-Responsive Element Binding Protein Activation after β Cell Stimulation by Glucose and Its Alteration Due to Glucotoxicity

Annals of the New York Academy of Sciences ◽

10.1196/annals.1329.029 ◽

2004 ◽

Vol 1030 (1) ◽

pp. 230-242 ◽

Cited By ~ 16

Author(s):

SAFIA COSTES ◽

CHRISTINE LONGUET ◽

CHRISTOPHE BROCA ◽

OMAR FARUQUE ◽

EL HABIB HANI ◽

...

Keyword(s):

Protein Kinase ◽

Mitogen Activated Protein Kinase ◽

Β Cell ◽

Cooperative Effects ◽

Protein Activation ◽

Mitogen Activated Protein ◽

Element Binding Protein ◽

Responsive Element ◽

Camp Responsive Element Binding ◽

Kinase A

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FGIN-1-27 Inhibits Melanogenesis by Regulating Protein Kinase A/cAMP-Responsive Element-Binding, Protein Kinase C-β, and Mitogen-Activated Protein Kinase Pathways

Frontiers in Pharmacology ◽

10.3389/fphar.2020.602889 ◽

2020 ◽

Vol 11 ◽

Author(s):

Jinpeng Lv ◽

Songzhou Jiang ◽

Ying Yang ◽

Ximei Zhang ◽

Rongyin Gao ◽

...

Keyword(s):

Protein Kinase ◽

The Body ◽

Tyrosinase Activity ◽

Mitogen Activated Protein Kinase ◽

Mushroom Tyrosinase ◽

Mitogen Activated Protein ◽

Element Binding Protein ◽

Responsive Element

FGIN-1-27 is a synthetic mitochondrial diazepam binding inhibitor receptor (MDR) agonist that has demonstrated pro-apoptotic, anti-anxiety, and steroidogenic activity in various studies. Here we report, for the first time, the anti-melanogenic efficacy of FGIN-1-27 in vitro and in vivo. FGIN-1-27 significantly inhibited basal and α-melanocyte-stimulating hormone (α-MSH)-, 1-Oleoyl-2-acetyl-sn-glycerol (OAG)- and Endothelin-1 (ET-1)-induced melanogenesis without cellular toxicity. Mushroom tyrosinase activity assay showed that FGIN-1-27 did not directly inhibit tyrosinase activity, which suggested that FGIN-1-27 was not a direct inhibitor of tyrosinase. Although it was not capable of modulating the catalytic activity of mushroom tyrosinase in vitro, FGIN-1-27 downregulated the expression levels of key proteins that function in melanogenesis. FGIN-1-27 played these functions mainly by suppressing the PKA/CREB, PKC-β, and MAPK pathways. Once inactivated, it decreased the expression of MITF, tyrosinase, TRP-1, TRP-2, and inhibited the tyrosinase activity, finally inhibiting melanogenesis. During in vivo experiments, FGIN-1-27 inhibited the body pigmentation of zebrafish and reduced UVB-induced hyperpigmentation in guinea pig skin, but not a reduction of numbers of melanocytes. Our findings indicated that FGIN-1-27 exhibited no cytotoxicity and inhibited melanogenesis in both in vitro and in vivo models. It may prove quite useful as a safer skin-whitening agent.

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