Cyclic AMP a Key Messenger in the Regulation of Skin Pigmentation

Buscà, Roser; Ballotti, Robert

doi:10.1034/j.1600-0749.2000.130203.x

Cited by 716 publications

(671 citation statements)

References 62 publications

Supporting

Mentioning

629

Contrasting

Unclassified

Order By: Relevance

“…The precise kinase(s) responsible for CREB/ATF1 phosphorylation are likely to include Rsk kinase (Bohm et al 1995) and/or Protein Kinase A. Other consequences of cAMP stimulation have also been suggested, including activation of RAF/MAPK (Busca and Ballotti 2000) and inhibition of the PI3K pathways (Khaled et al 2003), in addition to activation of the canonical PKA response. While CREB and ATF1 likely contribute directly to transcriptional regulation of certain components of the pigmentation machinery, it is probable that their activation of Mitf plays an important role as well, with Mitf likely imposing tissue-specific expression of these genes.…”

Section: Msh Signalingmentioning

confidence: 99%

Malignant melanoma: genetics and therapeutics in the genomic era

2006

View full text Add to dashboard Cite

Cell for cell, probably no human cancer is as aggressive as melanoma. It is among a handful of cancers whose dimensions are reported in millimeters. Tumor thickness approaching 4 mm presents a high risk of metastasis, and a diagnosis of metastatic melanoma carries with it an abysmal median survival of 6-9 mo. What features of this malignancy account for such aggressive behavior? Is it the migratory history of its cell of origin or the programmed adaptation of its differentiated progeny to environmental stress, particularly ultraviolet radiation? While the answers to these questions are far from complete, major strides have been made in our understanding of the cellular, molecular, and genetic underpinnings of melanoma. More importantly, these discoveries carry profound implications for the development of therapies focused directly at the molecular engines driving melanoma, suggesting that we may have reached the brink of an unprecedented opportunity to translate basic science into clinical advances. In this review, we attempt to summarize our current understanding of the genetics and biology of this disease, drawing from expanding genomic information and lessons from development and genetically engineered mouse models. In addition, we look forward toward how these new insights will impact on therapeutic options for metastatic melanoma in the near future. The diseaseMelanomas most often arise within epidermal melanocytes of the skin, although they can also derive from noncutaneous melanocytes such as those lining the choroidal layer of the eye, GI and GU mucosal surfaces, or the meninges. Melanoma is also among the more common causes of "metastatic cancer of unknown primary," which may reflect either a propensity to arise in unexpected sites along the neural crest migratory route, or rapid growth of poorly differentiated lesions arising from indolent or unrecognized cutaneous primary lesions. Clinical staging for primary cutaneous melanoma employs measurements of thickness (in millimeters), presence of ulceration, penetration through cutaneous layers, mitotic rate, evidence of "in transit" metastasis, tumor spread to draining lymph nodes, and evidence of distant metastasis. Management issues in melanoma can be classified in terms of prevention, diagnosis, local disease management, and treatment of metastatic disease.In view of the epidemiological and emerging experimental evidence linking melanoma incidence to UV exposure and skin phototype, prevention and screening strategies represent key areas for reduction of disease incidence and severity. For most cutaneous melanomas in the so-called radial growth phase (e.g., thin melanomas), surgical removal affords curative treatment. In contrast, a significant fraction of patients diagnosed with intermediate-thickness (2-4 mm) cutaneous melanoma eventually succumb to recurrence at regional or distant sites.Critical biological questions facing the melanoma research community include: (1) What genetic and environmental factors contribute to and/or modulate risk of melanom...

show abstract

Section: Msh Signalingmentioning

confidence: 99%

Malignant melanoma: genetics and therapeutics in the genomic era

2006

View full text Add to dashboard Cite

show abstract

“…MC1R binds its ligand, -MSH, and induces cAMP synthesis in melanocytes, leading to upregulation of melanogenesis. 21 E-box is present immediately upstream of the transcriptional initiation site. 28,29) The presence of an E-box suggests the possibility that MITF regulates Mc1r gene expression by the same transcriptional mechanism as Tyr and Trp1.…”

Section: Discussionmentioning

confidence: 99%

“…19,20) -MSH, a physiological ligand that binds to melanocortin-1 receptor (MC1R), potently induces expression of Mitf through the elevation of cyclic adenosine monophosphate (cAMP) levels, leading to increased expression of Tyr and other melanogenic enzymes, which ultimately increases melanin synthesis. 21) Elephantopus mollis H.B. and K. (Compositae) is known as ''peh-teng-khia-u'' in Formosan folklore and is used as a herbal remedy.…”

mentioning

confidence: 99%

Inhibitory Effect of Elephantopus mollis H.B. and K. Extract on Melanogenesis in B16 Murine Melanoma Cells by Downregulating Microphthalmia-Associated Transcription Factor Expression

Hasegawa

Furuya

Mizuno

et al. 2010

Bioscience, Biotechnology, and Biochemistry

View full text Add to dashboard Cite

In this study, the inhibitory effect of Elephantopus mollis H.B. and K. extract on melanogenesis in B16 murine melanoma cells was examined and possible mechanisms were elucidated. The melanin content in B16 cells decreased when they were treated with E. mollis extract. Inhibition was accompanied by reduced expression of tyrosinase (TYR) and tyrosinaserelated protein 1 (TRP1). Furthermore, the expression level of microphthalmia-associated transcription factor (MITF), a major transcriptional regulator of genes encoding melanogenic enzymes such as Tyr and Trp1, decreased as assessed by western blotting and quantitative reverse transcriptase polymerase chain reaction (RT-PCR). These results suggest that E. mollis extract reduces melanogenesis by downregulating Mitf expression, leading to reduced expression of Tyr and Trp1. In addition, melanocortin-1 receptor (MC1R) expression was downregulated by E. mollis extract, suggesting desensitization to -melanocyte-stimulating hormone ( -MSH) of cells treated with the extract.

show abstract

“…When increased cAMP has an effect on PKA, the cAMP response element binding protein (CREB) and the cAMP response element (CRE), located in the M promoter of the microphtalmia-associated transcription factor (MITF) gene, bind together (19). Cyclic AMP then undergoes melanogenesis, primarily via activation of MITF, thereby leading to induction of the expression of melanogenic enzymes (16). Increased expression of MITF leads to enhancement of the expression of genes for the melanogenic enzyme family, tyrosinase, TRP1, TRP2 and dopachrome tautomerase (DCT), which eventually stimulates melanin synthesis (20)(21)(22).…”

Section: Mangosteen Leaf Extract Increases Melanogenesis In B16f1 Melmentioning

confidence: 99%

“…UV-irradiation, a representative melanogenesis triggering factor, causes secretion of several melanogenic signaling delivery substances: proopiomelanocortin (POMC), a precursor of α-melanocyte stimulating hormone (α-MSH), a receptor of α-MSH; melanocortin-1 receptor (MC1R); melanogenic enzymes; tyrosinase; tyrosinase-related protein-1 (TRP1); protein kinase C (PKC) from melanocyte (12,13). In human epidermis, once α-MSH and adrenocorticotropic hormone (ACTH) are produced and released by keratinocytes after UV-irradiation (14,15), they combine with their specific receptor MC1R and activate adenyl cyclase through G-protein, which converts adenosine triphosphate (ATP) to cyclic adenosine monophosphate (cAMP), leading to an increase in intracellular cAMP levels (16,17). Cyclic AMP, generated from ATP, plays a role as a second messenger in the intracellular signaling pathway (18).…”

Section: Mangosteen Leaf Extract Increases Melanogenesis In B16f1 Melmentioning

confidence: 99%

Mangosteen leaf extract increases melanogenesis in B16F1 melanoma cells by stimulating tyrosinase activity in vitro and by up-regulating tyrosinase gene expression

2011

View full text Add to dashboard Cite

Abstract. Melanin synthesis is stimulated by various effectors, including α-melanocyte stimulating hormone (α-MSH), cyclic AMP (cAMP)-elevating agents (forskolin, isobutylmethylxantine, glycyrrhizin) and ultraviolet light. Our investigation focused on the identification of the melanogenic efficacy of mangosteen (Garcinia mangostana) leaf extract with regard to its effects on melanogenesis in B16F1 melanoma cells, since it has been known to possess strong anti-oxidant activities. The mangosteen leaf extract was found to stimulate melanin synthesis and tyrosinase activity in a dose-dependent manner without any significant effects on cell proliferation. Cytotoxicity of the extract was measured using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay; the highest concentration of the extract that did not affect cell viability was 32 µg/ml. Formation of melanin from cultured B16F1 melanoma induced by extract treatment was estimated using spectrophotometry. In order to clarify the subsequent mechanism of tyrosinase activation by the extract, the levels of tyrosinase expression in B16F1 melanoma were examined using an intracellular tyrosinase assay and tyrosinase zymography. Up-regulation of intracellular tyrosinase expression seemed to correlate with an increase in microphtalmia-associated transcription factor (MITF) protein levels since MITF is the key factor for genes involved in melanogenesis. Both of the results showed that tyrosinase activity was markedly enhanced from extract-treated cells. The overall results suggest that mangosteen leaf extract may be a promising candidate for the treatment of hypopigmentation disorder and useful for selftanning cosmetic products.

show abstract

Cyclic AMP a Key Messenger in the Regulation of Skin Pigmentation

Cited by 716 publications

References 62 publications

Malignant melanoma: genetics and therapeutics in the genomic era

Malignant melanoma: genetics and therapeutics in the genomic era

Inhibitory Effect of Elephantopus mollis H.B. and K. Extract on Melanogenesis in B16 Murine Melanoma Cells by Downregulating Microphthalmia-Associated Transcription Factor Expression

Mangosteen leaf extract increases melanogenesis in B16F1 melanoma cells by stimulating tyrosinase activity in vitro and by up-regulating tyrosinase gene expression

Contact Info

Product

Resources

About