9‐<i>cis</i> retinoic acid is the <scp>ALDH</scp>1<scp>A</scp>1 product that stimulates melanogenesis

Paterson, Elyse K.; Ho, Hsiang‐Ling; Kapadia, Rubina; Ganesan, Anand K.

doi:10.1111/exd.12099

Cited by 35 publications

(41 citation statements)

References 66 publications

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“…ALDH genes have recently been shown to stimulate melanogenesis by impacting the expression of MITF (Paterson et al . ), a central regulatory element of the melanogenesis pathway.…”

Section: Resultsmentioning

confidence: 99%

Transcriptomics of colour patterning and coloration shifts in crows

et al. 2015

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Animal coloration is one of the most conspicuous phenotypic traits in natural populations and has important implications for adaptation and speciation. Changes in coloration can occur over surprisingly short evolutionary timescales, while recurrence of similar colour patterns across large phylogenetic distances is also common. Even though the genetic basis of pigment production is well understood, little is known about the mechanisms regulating colour patterning. In this study, we shed light on the molecular elements regulating regional pigment production in two genetically near-identical crow taxa with striking differences in a eumelanin-based phenotype: black carrion and grey-coated hooded crows. We produced a high-quality genome annotation and analysed transcriptome data from a 2 × 2 design of active melanogenic feather follicles from head (black in both taxa) and torso (black in carrion and grey in hooded crow). Extensive, parallel expression differences between body regions in both taxa, enriched for melanogenesis genes (e.g. ASIP, CORIN, and ALDH6), indicated the presence of cryptic prepatterning also in all-black carrion crows. Meanwhile, colour-specific expression (grey vs. black) was limited to a small number of melanogenesis genes in close association with the central transcription factor MITF (most notably HPGDS, NDP and RASGRF1). We conclude that colour pattern differences between the taxa likely result from an interaction between divergence in upstream elements of the melanogenesis pathway and genes that provide an underlying prepattern across the body through positional information. A model of evolutionary stable prepatterns that can be exposed and masked through simple regulatory changes may explain the phylogenetically independent recurrence of colour patterns that is observed across corvids and many other vertebrate groups.

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“…ALDH genes have recently been shown to stimulate melanogenesis by impacting the expression of MITF (Paterson et al . ), a central regulatory element of the melanogenesis pathway.…”

Section: Resultsmentioning

confidence: 99%

Transcriptomics of colour patterning and coloration shifts in crows

et al. 2015

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“…The authors now show that 9‐ cis retinal in conjugation with UV radiation enhances significantly the accumulation of both MITF and TYR mRNA, leading to increased melanin deposition. In addition, the metabolic product of 9‐ cis retinal oxidation, 9‐ cis retinoic acid, also increased melanin accumulation . Paterson et al.…”

Section: Commentarymentioning

confidence: 98%

“…However, inhibitors of ALDH1A1 such as cyanamide or Angeli's salt dramatically suppress melanin accumulation in skin specimen containing normal human epidermal keratinocytes and melanocytes and significantly decrease MITF and TYR mRNA accumulation at relatively small concentrations . This suggests that ALDH1A1 is a key enzyme in the regulation of skin pigmentary responses mediated by retinoids (Fig.…”

Section: Commentarymentioning

confidence: 99%

Targeting ALDH1A1 to treat pigmentary disorders

Kleszczyński

Slominski

2013

Experimental Dermatology

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Clinical disorders related to skin pigmentation include hypo- or hyperpigmentation. Because they are difficult to treat, new approaches to develop safe pigment modulatory agents are needed. In this issue, Paterson et al. (1) determined which aldehyde dehydrogenase 1A1 (ALDH1A1) substrates and products regulate melanogenesis. The authors demonstrated that ALDH1A1 substrate 9-cis retinal and its corresponding product 9-cis retinoic acid potently induced the accumulation of MITF mRNA, tyrosinase mRNA, and melanin. Despite depletion of ALDH1A1 there was observed decreased ability of 9-cis retinal but not 9-cis retinoic acid to stimulate melanogenesis, indicating that ALDH1A1 regulates melanogenesis by catalyzing the conversion of 9-cis retinal to 9-cis retinoic acid. Additionally, potent ALDH1A1 inhibitor such as cyanamide or Angeli’s salt significantly suppressed pigmentation in human skin cells. These findings provide new candidate agents for the treatment of hypo- or hyperpigmentation disorders, using novel pigmentation-modulatory agents that target ALDH1A1.

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“…Intracellular retinoid levels are regulated by mechanisms that are not completely understood [5,6]. For ATRA synthesis, vitamin A (all- trans -retinol, ATRol) can be oxidated via all- trans -retinal (ATRal) as a metabolic intermediate [7,8]. Due to the antiproliferative and prodifferentiation effects of ATRA [9], it is successfully used to treat several types of cancers [10,11].…”

Section: Introductionmentioning

confidence: 99%

LRAT Overexpression Diminishes Intracellular Levels of Biologically Active Retinoids and Reduces Retinoid Antitumor Efficacy in the Murine Melanoma B16F10 Cell Line

Amann

Czaja

Bazhin

et al. 2015

Skin Pharmacol Physiol

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Background/Aim: Vitamin A (all-trans-retinol, ATRol) serves as a precursor for all-trans-retinoic acid (ATRA), a ligand for the retinoic acid receptor (RAR), representing a potent regulator for many physiological processes. While murine melanoma cells are highly sensitive to retinoid treatment, human melanoma cells have developed still unidentified mechanisms that mediate cellular retinoid resistance. One of the key retinoid metabolizing enzymes is lecithin retinol acyltransferase (LRAT), which catalyzes the transformation of ATRol into inactive retinyl esters. LRAT is highly expressed in human melanoma cells. The aim of this study was to identify the mechanisms in retinol metabolism that are responsible for cellular retinoid sensitivity in the murine melanoma cell line B16F10. Methods: mRNA expression analysis, cell viability assessment and determination of intracellular retinoid levels using HPLC analysis of a generated LRAT-overexpressing B16F10 cell line compared to the control B16F10 cell line. Results: We found that the murine retinoid-sensitive B16F10 cell line does not express the enzyme LRAT. LRAT overexpression decreased the antiproliferative effects of retinoid treatment in these melanoma cells. The RAR-regulated enzyme Cyp26a1 showed a significantly lower expression in LRAT-overexpressing B16F10 cells. Cyp26a1 expression was restored after ATRA incubation. HPLC analysis revealed that the level of inactive retinyl ester increased after ATRol treatment, and levels of the substrate ATRol and biologically active ATRA significantly decreased in LRAT-overexpressing murine melanoma. Consistently with this, levels of 4-oxo-retinoic acid, an ATRA metabolite and Cyp26a1 product, were also decreased in LRAT-overexpressing cells. Conclusion: Our results revealed a direct link between LRAT expression and regulation of ATRA levels indicating that the absence of LRAT-catalyzed retinol esterification is important for mediating retinoid sensitivity in murine melanoma cells. Thus, our data suggest that LRAT overexpression represents a novel mechanism by which tumor cells can escape high supplementary ATRA levels that mediate tumor-suppressive RAR signaling.

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9‐cis retinoic acid is the ALDH1A1 product that stimulates melanogenesis

Cited by 35 publications

References 66 publications

Transcriptomics of colour patterning and coloration shifts in crows

Transcriptomics of colour patterning and coloration shifts in crows

Targeting ALDH1A1 to treat pigmentary disorders

LRAT Overexpression Diminishes Intracellular Levels of Biologically Active Retinoids and Reduces Retinoid Antitumor Efficacy in the Murine Melanoma B16F10 Cell Line

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