Signalling mechanisms of endothelin-induced mitogenesis and melanogenesis in human melanocytes

Imokawa, Genji; Yada, Yukihiro; Kimura, Mitsutoshi

doi:10.1042/bj3140305

Cited by 155 publications

(171 citation statements)

References 45 publications

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“…DAG has been reported to activate MAPK via protein kinase C. The action of ET-1 is transmitted to stimulate cell proliferation mainly via MAPK. 9,20) The present study showed that the extract of A. officinalis did not affect the intracellular signal transduction pathway located upstream of calcium mobilization, i.e., the binding of ET-1 to the ET B R on NHMC or the production of IP 3 . In contrast, the ET-1-induced activation of MAPK was inhibited by the extract.…”

Section: Discussionmentioning

confidence: 86%

Inhibitory Mechanism of an Extract of Althaea officinalis L. on Endothelin-1-Induced Melanocyte Activation.

Kobayashi

Hachiya

Ohuchi

et al. 2002

Biological & Pharmaceutical Bulletin

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When the skin is irradiated with UVB light, various cytokines are released, act on normal human melanocytes (NHMC), and induce them to synthesize melanin pigment, to proliferate and to differentiate, which leads to increased pigmentation.1-3) Endothelin-1 (ET-1), 2,4) basic fibroblast growth factor (b-FGF), 5) and a-melanocyte-stimulating hormone, [6][7][8] all of which are produced by normal human keratinocytes (NHKC) and are up-regulated following UVB irradiation, act as mitogens for NHMC. Furthermore, an increase in ET-1 expression 3) in human skin after UVB irradiation has also been reported, and it has been suggested that ET-1 plays an important role in UVB-induced pigmentation. Therefore, we have investigated various botanical extracts that inhibit the ET-1-induced activation of NHMC. Since intracellular calcium mobilization is induced when ET-1 acts on NHMC, 1) we have continued to search for new agents which can block this calcium mobilization and we have found that an extract of Althaea officinalis L. has a potent inhibitory effect. In this study, we have clarified the inhibitory mechanism of the extract of A. officinalis on ET-1-induced activation of NHMC. MATERIALS AND METHODS Extract of A. officinalis L.A. officinalis is a large perennial plant belonging to the genus hollyhock in the mallow family. Pale pink hollyhock, velvet hollyhock, and marshmallow also belong to this family, and A. officinalis is cultivated for gardening, medication, and food in Europe. The genus name 'Althaea' is derived from 'althaino' in Greek, meaning therapy. The species name 'officinalis' means 'use for drug', and the plant is often prescribed for pain relief and treatment of renal function, inflammation, and irritation syndrome. The portions of the plant used as a drug are the roots and leaves that contain abundant mucus. Marshmallow sweet was originally sipped to treat sore throats, and can be jelled by soaking the root powder with sugar in water. We extracted A. officinalis roots with a 45% 1,3-butylene glycol solution and obtained a brown transparent extract, which was used in this evaluation.Materials NHMC were obtained from KURABO Industries, Ltd. (Osaka, Japan) and NHKC were obtained from Sanko Junyaku Co., Ltd. (Tokyo, Japan). Serum-free NHMC medium (MGM) was purchased from Sanko Pure Chemicals (Tokyo, Japan) and serum-free NHKC medium (SFM) and Dulbecco's modified Eagle's medium (DMEM) were purchased from Gibco Laboratories (Grand Island, NY, U.S.A.). ET derivatives were purchased from Wako Pure Chemical Industries, Ltd. (Tokyo, Japan). Other chemicals were of reagent grade.Cell Culture NHMC were maintained in MGM supplemented with 1 ng/ml recombinant b-FGF, 0.5 mg/ml hydrocortisone, 5 mg/ml insulin, 10 ng/ml phorbol 12-myristate 13-acetate, 3 mg/ml heparin, antibiotics (50 mg/ml streptomycin), and 0.2% bovine pituitary extract (BPE). NHKC were maintained in modified SFM supplemented with 5 ng/ml epidermal growth factor and 50 mg/ml BPE. B16 F10 melanoma cells are a subline of the pigmented B16 melanoma (C57BL/6N)...

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Section: Discussionmentioning

confidence: 86%

Inhibitory Mechanism of an Extract of Althaea officinalis L. on Endothelin-1-Induced Melanocyte Activation.

Kobayashi

Hachiya

Ohuchi

et al. 2002

Biological & Pharmaceutical Bulletin

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“…This is in sharp contrast to Kit-null mutant mouse, which displays severe loss of melanocytes (Cable et al, 1995;Mayer, 1979;Russell, 1979). Interestingly, engineered Kit-null neural crest cultures can sustain melanoblast survival (Hou et al, 2000) through activation of the endothelin pathway that converges with the MAPK pathway like that of Kit (Imokawa et al, 1996). Furthermore, heterozygosity of the tumor-suppressor neurofibrinogen-1, a known negative regulator of RAS-MAPK pathway, gives a partial rescue of Kit-mutations in the mouse (Ingram et al, 2001).…”

Section: Mitf Guards Survival Of Melanocytes and Melanoma Cellsmentioning

confidence: 99%

“…ET-3 and its receptor, Ednrb, are required for normal differentiation and development of melanocytes and Auerbach plexus cells, the enteric ganglia of the gut (for a review see McCallion and Chakravarti, 2001). Ednrb is a G-protein-coupled receptor of the seven-transmembrane family that is thought to modulate cAMP levels (Fuchs et al, 2001) and activate the RAS-MAP-kinase pathway (Imokawa et al, 1996). The temporal need for Ednrb in melanocyte and enteric ganglia has been elegantly examined using engineered mice (Shin et al, 1999) in which inducible expression of Ednrb identified a critical period between embryonic days 10 and 12.5 for the development of these two lineages.…”

Section: Mitf-m Is Critical For the Melanocyte Fate In The Neural Crementioning

confidence: 99%

Microphthalamia-associated transcription factor: a critical regulator of pigment cell development and survival

2003

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The microphthalamia-associated transcription factor (MITF) is an integral transcriptional regulator in melanocyte, the lineage from which melanoma cells originate. This basic-helix-loop-helix-leucine-zipper (bHLHzip) protein is critical for melanocyte cell-fate choice during commitment from pluripotent precursor cells in the neural crest. Its role in differentiation pathways has been highlighted by its potent transcriptional and lineage-specific regulation of the three major pigment enzymes: tyrosinase, Tyrp1, and Dct as well as other pigmentation factors. However, the cellular functions of MITF seem to be wider than differentiation and cell-fate pathways alone, since melanocytes and melanoma cells appear to require an expression of this factor. Here, we discuss the transcriptional networks in which MITF is thought to reside and describe signaling pathways in the cell which impinge on MITF. Accumulating evidence supports the notion that MITF is involved in survival pathways during normal development as well as during neoplastic growth of melanoma.

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“…Melanocyte dendrite formation is regulated through multiple signaling pathways stimulated by paracrine factors released by keratinocytes in response to UVR [11][12][13]. In human melanocytes the balance between Rac and Rho activation is a strong determinant of melanocyte dendrite formation [14][15][16][17].…”

Section: Introductionmentioning

confidence: 99%

Prostaglandin E2 regulates melanocyte dendrite formation through activation of PKCζ

Scott

Fricke

Fender

et al. 2007

Experimental Cell Research

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Prostaglandins are lipid signaling intermediates released by keratinocytes in response to ultraviolet irradiation (UVR) in the skin. The main prostaglandin released following UVR is PGE 2 , a ligand for 4 related G-protein coupled receptors (EP 1 , EP 2 , EP 3 and EP 4 ). Our previous work established that PGE 2 stimulates melanocyte dendrite formation through activation of the EP 1 and EP 3 receptors. The purpose of the present report is to define the signaling intermediates involved in EP 1 and EP 3 -dependent dendrite formation in human melanocytes. We recently showed that activation of the atypical PKCζ isoform stimulates melanocyte dendricity in response to treatment with lysophosphatidylcholine. We therefore examined the potential contribution of PKCζ activation on EP 1 and EP 3 -dependent dendrite formation in melanocytes. Stimulation of the EP 1 and EP 3 receptors by selective agonists activated PKCζ, and inhibition of PKCζ activation abrogated EP 1 and EP 3 -receptor mediated melanocyte dendricity. Because of the importance of Rho-GTP binding proteins in the regulation of melanocyte dendricity, we also examined the effect of EP 1 and EP 3 receptor activation on Rac and Rho activity. Neither Rac nor Rho was activated upon treatment with EP 1,3 -receptor agonists. We show that melanocytes express only the EP 3A1 isoform, but not the EP 3B receptor isoform, previously associated with Rho activation, consistent with a lack of Rho stimulation by EP 3 agonists. Our data suggest that PKCζ activation plays a predominant role in regulation of PGE 2 -dependent melanocyte dendricity.

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Signalling mechanisms of endothelin-induced mitogenesis and melanogenesis in human melanocytes

Cited by 155 publications

References 45 publications

Inhibitory Mechanism of an Extract of Althaea officinalis L. on Endothelin-1-Induced Melanocyte Activation.

Inhibitory Mechanism of an Extract of Althaea officinalis L. on Endothelin-1-Induced Melanocyte Activation.

Microphthalamia-associated transcription factor: a critical regulator of pigment cell development and survival

Prostaglandin E2 regulates melanocyte dendrite formation through activation of PKCζ

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