Tyrosinase isoenzymes in mammalian melanocytes

Jiménez‐Cervantes, Celia; García‐Borrón, José C.; Valverde, Paloma; Solano, Francisco; Lozano, José Antonio

doi:10.1111/j.1432-1033.1993.tb18276.x

Cited by 89 publications

(66 citation statements)

References 37 publications

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“…2). The effect was apparently mediated by high affinity receptors, since the inhibition was evident at concentrations as low as 10 Ϫ12 M and 50% inhibitions were observed at 10 Ϫ11 M. The cytokine inhibited the Dopa oxidase (and probably the tyrosine hydroxylase) activity of the two tyrosinase isoenzymes, tyrosinase and TRP-1, as shown by electrophoretic separation followed by activity stain (25,35) (Fig. 3).…”

Section: Effect Of Epidermal Cytokines On the Melanogenicmentioning

confidence: 99%

Transforming Growth Factor-β1 Inhibits Basal Melanogenesis in B16/F10 Mouse Melanoma Cells by Increasing the Rate of Degradation of Tyrosinase and Tyrosinase-related Protein-1

Martínez‐Esparza

Jiménez‐Cervantes

Beermann³

et al. 1997

Journal of Biological Chemistry

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Current evidence suggests that melanogenesis is controlled by epidermal paracrine modulators. We have analyzed the effects of transforming growth factor-␤1 (TGF-␤1) on the basal melanogenic activities of B16/F10 mouse melanoma cells. TGF-␤1 treatment (48 h) elicited a concentration-dependent decrease in basal tyrosine hydroxylase and 3,4-dihydroxyphenylalanine (Dopa) oxidase activities, to less than 30% of the control values but had no effect on dopachrome tautomerase activity (TRP-2). The inhibition affected to similar extents the Dopa oxidase activity associated to tyrosinase-related protein-1 (TRP-1) and tyrosinase. This inhibition was noticeable between 1 and 3 h after the addition of the cytokine, and maximal after 6 h of treatment. The decrease in the enzymatic activity was paralleled by a decrease in the abundance of the TRP-1 and tyrosinase proteins. TGF-␤1 mediated this effect by increasing the rate of degradation of tyrosinase and TRP-1. Conversely, after 48 h of treatment, the expression of the tyrosinase gene decreased only slightly, while TRP-1 and TRP-2 gene expression was not affected. An increased rate of proteolytic degradation of TRP-1 and tyrosinase seems the main mechanism accounting for the inhibitory effect of TGF-␤1 on the melanogenic activity of B16/F10 cells.Melanin pigmentation in mammals is a highly regulated and complex event occurring within specialized cells, the melanocytes (1-3). The pathway starts by two reactions catalyzed by tyrosinase (monophenol monooxygenase, EC 1.14.18.1), the hydroxylation of L-tyrosine to L-Dopa, 1 and the oxidation of LDopa to dopaquinone. In the absence of thiolic compounds, dopaquinone evolves spontaneously to L-dopachrome, and then to melanin. Two other enzymes, TRP-1 and TRP-2, have been shown to participate in the process. TRP-2, also called DCT (EC 5.3.2.3.), catalyzes the non-decarboxylative rearrangement of L-dopachrome to 5,6-dihydroxyindole-2-carboxylic acid (4 -6). This stable diphenol is oxidized by TRP-1 to an unstable oquinone that undergoes further polymerization reactions to yield melanin (7,8). Moreover, other melanosomal proteins such as pmel 17 could also be involved in the control of the distal melanogenic reactions (9, 10). Tyrosinase itself could also participate in other oxidative steps, thus enhancing the polymerization rate of melanogenic intermediates (11,12).Due to the high reactivity of the melanogenic intermediates, melanogenesis is confined in specialized organelles called melanosomes. Epidermal melanization involves not only the synthesis of the pigment but also the transfer of melanized melanosomes to the keratinocytes surrounding the dendritic processes of melanocytes. Thus, melanocytes are in intimate physical and functional contact with other epidermal cells, which could contribute to the control of the melanogenic status of melanocytes through the secretion of several cytokines and paracrine factors. In keeping with this view, the skin contains a variety of chemical messengers with the potential to affect the prolifer...

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Section: Effect Of Epidermal Cytokines On the Melanogenicmentioning

confidence: 99%

Transforming Growth Factor-β1 Inhibits Basal Melanogenesis in B16/F10 Mouse Melanoma Cells by Increasing the Rate of Degradation of Tyrosinase and Tyrosinase-related Protein-1

Martínez‐Esparza

Jiménez‐Cervantes

Beermann³

et al. 1997

Journal of Biological Chemistry

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“…We have previously shown that the HEMT and LEMT proteins display different tyrosine hydroxylase/dopa oxidase activity ratios [24]. As shown in Fig.…”

Section: Differential Effect Of Melanogenic Activators On the Tyrosinmentioning

confidence: 80%

“…Since we have previously shown that the LEMT and HEMT proteins can be resolved by electrophoresis [24], the isoenzymatic pattern of melanosomal preparations obtained from control cells and those treated with MSH or theophylline was analyzed by SDSPAGE. As shown in Fig.…”

Section: Electrophoretic Demonstration Of the Preferential Induction mentioning

confidence: 99%

“…It has also been shown that treatment with MSH might result in a different degree of stimulation of two still uncharacterized tyrosinases in B16 mouse melanoma melanocytes 1171 with larger increases in the tyrosine hydroxylase than in the dopa oxidase activity. These observations led us to examine the possibility that malignant melanocytes might respond to MSH with low to moderate percentage increases in the expression of the LEMT protein, and large percentage increases in the expression of the HEMT protein [24]. Owing to the difference in specific activities of both proteins, a relatively small absolute increase in the expression of the HEMT protein would result in a much larger percentage increase in the total tyrosinase activity of the cell.…”

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confidence: 99%

“…Taking advantage of the knowledge of the physicochemical and kinetic properties of the LEMT and HEMT proteins [24], we have investigated the distribution of tyrosinase isoenzymes in B16 mouse melanocytes upon stimulation by MSH and other melanogenic agents. We show that, under basal conditions, B16 melanocytes express almost exclusively the LEMT, but that they do indeed respond to MSH with higher increases in the expression of the HEMT protein, as opposed to LEMT.…”

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confidence: 99%

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Tyrosinase isoenzymes in mammalian melanocytes

Valverde

García‐Borrón

Jiménez‐Cervantes

et al. 1993

European Journal of Biochemistry

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In mouse melanoma melanocytes, a-melanocyte-stimulating hormone (MSH) stimulates differentiation, melanin synthesis and tyrosinase activity. However, the molecular mechanisms underlying these events have not yet been characterized. We have studied the activation of tyrosinase by MSH. Treatment of B16 melanoma cells with either theophylline, MSH, or its superpotent analog [Ahx4, ~P h e~l M s H promotes a larger induction of tyrosine hydroxylase than of dopa oxidase activity in whole cell extracts. This higher activation of tyrosine hydroxylation was found not only in the melanosomal but also in the microsomal fraction; it appears to be dependent on continued transcription and translation since it can be blocked by actinomycin and cycloheximide. The tyrosinase activity of control and theophylline-treated extracts displayed several kinetic differences, including different K,, values for both substrates and requirements for the cofactor L-dopa. SDSPAGE, followed by a sensitive specific activity stain, demonstrated that melanosomes of control cells contain one lower-electrophoretic-mobility form of tyrosinase, whereas melanosomes of cells treated with either theophylline or MSH display, in addition to the lower-mobility form, a faster-migrating activity band. These tyrosinase forms are not interconvertible by proteolysis or deglycosylation. Their nature is discussed as related to the properties of the previously described low-and high-electrophoretic-mobility tyrosinases (LEMT and HEMT), as well as of the proteins encoded by the c and b loci.Tyrosinase (monophenol monooxygenase) is the enzyme controling the rate-limiting step in melanin biosynthesis, the hydroxylation of L-tyrosine to 3,4-dihydroxy-~-phenylalanine (1-dopa) [l, 21. A variety of mammalian melanocytes in culture have been shown to respond to treatment with a-melanocyte-stimulating hormone (MSH) with large increases in tyrosinase activity, leading ultimately to a visible increase in the amount of pigment formed within the cells Enzyme. Tyrosinase, monophenol monooxygenase (EC 1.14.18.1).161 are able to mimick the hormone action, and even to achieve larger activations of the enzyme. However, the molecular mechanisms coupling the increase in intracellular cAMP to tyrosinase activation are unknown, and several possible explanations have been proposed. This increase might just reflect an increased tyrosinase abundance within stimulated cells [16, 181, or might result from two complementary processes, one leading to an increase in tyrosinase abundance and the other to the activation of a pre-existing pool of inactive tyrosinase molecules [9, 19, 201. According to this last hypothesis, only moderate increases in tyrosinase mRNA levels [21, 221 and in the rates of synthesis and degradation of the protein [9, 201 have been detected in MSHstimulated cells. However, continued transcription and translation has been reported to be essential for tyrosinase activation [9].On the other hand, it has been shown that mouse, and possibly human, melanocytes contain two tyr...

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Enzymology of Melanin Formation

Solano¹,

García‐Borrón²

2006

The Pigmentary System

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Tyrosinase isoenzymes in mammalian melanocytes

Cited by 89 publications

References 37 publications

Transforming Growth Factor-β1 Inhibits Basal Melanogenesis in B16/F10 Mouse Melanoma Cells by Increasing the Rate of Degradation of Tyrosinase and Tyrosinase-related Protein-1

Transforming Growth Factor-β1 Inhibits Basal Melanogenesis in B16/F10 Mouse Melanoma Cells by Increasing the Rate of Degradation of Tyrosinase and Tyrosinase-related Protein-1

Tyrosinase isoenzymes in mammalian melanocytes

Enzymology of Melanin Formation

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