Tyrosine hydroxylase isoenzyme I is present in human melanosomes: a possible novel function in pigmentation

Marles, Lee K.; Peters, Eva M.J.; Tobin, Desmond J.; Hibberts, Nigel A.; Schallreuter, Karin U.

doi:10.1034/j.1600-0625.2003.120108.x

Cited by 58 publications

(75 citation statements)

References 43 publications

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“…However, it must be noted that the presence of 7BH 4 in melanosomes also implicates 6BH 4 in this organelle, since the 7-isomer is only produced by the aromatic amino acid hydroxylases from 6BH 4 via 4a-OH-carbinolamine in the absence of PCD (Curtius et al 1990a, Adler et al 1992. It is noteworthy that the presence of tyrosine hydroxylase isoform I (TH) has been demonstrated in melanosomes while PAH is absent in this organelle (Marles et al 2003). Whether the third hydroxylase, i.e.…”

Section: Discussionmentioning

confidence: 99%

A novel mechanism in control of human pigmentation by β-melanocyte-stimulating hormone and 7-tetrahydrobiopterin

Spencer¹,

Chavan²,

Marles³

et al. 2005

Journal of Endocrinology

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The human skin holds the full machinery for proopiomelanocortin processing. The -melanocytestimulating hormone ( -MSH)/melanocortin-1-receptor cascade has been implicated as a major player via the cAMP signal in the control of melanogenesis. Only very recently the -endorphin/µ-opiate receptor signal has been added to the list of regulators of melanocyte dendricity and melanin formation. In this context it was reported that (6R)--erythro-5,6,7,8-tetrahydrobiopterin (6BH 4 ) can act as an allosteric inhibitor of tyrosinase, the key enzyme in melanogenesis, and this inhibition is reversible by both -and -MSH. It was also shown earlier that 7BH 4 , the isomer of 6BH 4 , is twice as active in this inhibition reaction. However, as yet it is not known whether 7BH 4 is indeed present in loco in the melanosome. We here provide evidence that this isomer is present in this organelle in a concentration range up to 50 10 6 M. Determination of -MSH in melanosomal extracts yielded 10 pg/mg protein. Moreover, we demonstrate reactivation of the 7BH 4 /tyrosinase inhibitor complex by -MSH, whereas -MSH failed to do so. Furthermore, we show intra-melanosomal -dopa formation from dopachrome by 7BH 4 in a concentration range up to 134 10 6 M. Based on these results, we propose a new receptorindependent mechanism in the control of tyrosinase/ melanogenesis by -MSH and the pterin 7BH 4 .

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Section: Discussionmentioning

confidence: 99%

A novel mechanism in control of human pigmentation by β-melanocyte-stimulating hormone and 7-tetrahydrobiopterin

Spencer¹,

Chavan²,

Marles³

et al. 2005

Journal of Endocrinology

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“…Vol. 66,2009 Review Article 1495 in melanosomes and to catalyze L-dopa synthesis, thus activating tyrosinase [47]. In addition, the enzyme phenylalanine hydroxlyase can contribute to tyrosinase activation because it catalyzes the conversion of L-phenylalanine to L-tyrosine, providing a substrate for tyrosinase [35].…”

Section: Bmp-4 Flmentioning

confidence: 99%

Cellular mechanisms regulating human melanogenesis

Park

Kosmadaki

Yaar

et al. 2009

Cell. Mol. Life Sci.

315

354

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The major differentiated function of melanocytes is the synthesis of melanin, a pigmented heteropolymer that is synthesized in specialized cellular organelles termed melanosomes. Mature melanosomes are transferred to neighboring keratinocytes and are arranged in a supranuclear cap, protecting the DNA against incident ultraviolet light (UV) irradiation. The synthesis and distribution of melanin in the epidermis involves several steps: transcription of melanogenic proteins, melanosome biogenesis, sorting of melanogenic proteins into the melanosomes, transport of melanosomes to the tips of melanocyte dendrites and finally transfer into keratinocytes. These events are tightly regulated by a variety of paracrine and autocrine factors in response to endogenous and exogenous stimuli, principally UV irradiation.

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“…Tyrosinase can also be indirectly activated by tyrosine hydroxylase isoenzyme 1 (TH1) as it that has been shown to be present in melanosomes and catalyzes L-dopa synthesis [21]. In turn, L-dopa can act as a cofactor for tyrosinase [22].…”

Section: Melanogenesismentioning

confidence: 99%

The melanogenesis and mechanisms of skin‐lightening agents – existing and new approaches

Gillbro¹,

Olsson²

2011

Intern J of Cosmetic Sci

307

251

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SynopsisSkin-lightening products are commercially available for cosmetic purposes to obtain lighter skin complexion. Clinically, they are also used for treatment of hyperpigmentary disorders such as melasma, café au lait spot and solar lentigo. All of these target naturally melanin production, and many of the commonly used agents are known as competitive inhibitors of tyrosinase, one of the key enzymes in melanogenesis. In this review, we present an overview of commonly used skin-whitening ingredients that are commercialized, but we also hypothesize on other mechanisms that could be important targets to control skin pigmentation such as for example regulation of the adrenergic and glutaminergic signalling and also control of tetrahydrobiopterins in the human skin. Ré suméLes produits éclaircissants sont disponibles dans le commerce pour des buts cosmétiques afin d'obtenir un tient plus clair. Ils sont égale-ment utilisés en clinique, pour le traitement de troubles hyper pigmentaires comme le melasma, les taches café au lait et le lentigo solaire. Tous ces produits ont pour cible la production naturelle de mélanine et beaucoup de ceux généralement utilisés sont reconnus comme des inhibiteurs compétitifs de la tyrosinase, une des enzymes clés de la mélanogénèse. Dans cette revue, nous présentons une vue d'ensemble des ingrédients généralement utilisés et commercialisés comme blanchissant cutanés mais nous formulons aussi l'hypothèse que d'autres mécanismes pourraient être des cibles importantes pour contrôler la pigmentation de la peau comme par exemple la régula-tion du signal adrénergique et glutaminergique ou le contrôle des tetrahydrobiopterines dans la peau humaine.

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Tyrosine hydroxylase isoenzyme I is present in human melanosomes: a possible novel function in pigmentation

Cited by 58 publications

References 43 publications

A novel mechanism in control of human pigmentation by β-melanocyte-stimulating hormone and 7-tetrahydrobiopterin

A novel mechanism in control of human pigmentation by β-melanocyte-stimulating hormone and 7-tetrahydrobiopterin

Cellular mechanisms regulating human melanogenesis

The melanogenesis and mechanisms of skin‐lightening agents – existing and new approaches

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