Melanocyte-stimulating hormone promotes activation of pre-existing tyrosinase molecules in Cloudman S91 melanoma cells

Wong, Glenda L.; Pawelek, John M.

doi:10.1038/255644a0

Cited by 149 publications

(63 citation statements)

References 6 publications

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“…However, there is no agreement as to whether the increase in tyrosinase activity is mainly a function of enzyme abundance [3,4], or reflects both an increased amount of tyrosinase and an activation of previously existing molecules [5], or even the activation of an inactive enzyme pool with little, if any, effect on the rate of enzyme synthesis [6]. As far as the activation of pre-existing tyrosinase molecules is concerned, both the cAMP-mediated removal of an inhibitor [7] or synthesis of an activator [5] have been postulated, although no clear-cut evidence has ever been put forward.…”

Section: I Introductionmentioning

confidence: 99%

Melanocyte stimulating hormone activation of tyrosinase in B16 mouse melanoma cells Evidence for a differential induction of two distinct isoenzymes

et al. 1992

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Tyrosinase induction in murine malignant melanoeytes by gMSH is well known, but its molecular basis has not been characterized. Treatment of BI6 melanoma cells with theophylline or rrMSH mediates a larger induction of tyrosine hydroxylase than of dopa oxidase activity in total cell extracts, and in the melanosomal and microsomal fractions. No evidence for the modulation of a tyrosinase effector was found. SDS-PAGE and slY~ific activity stain demonstrated two forms of tyro.,i~ase, with different degrees of induction by theophylline. These results agree with the recent proposal that two tyrosinases, encoded by different genes, are present in murine melanoeytes. cells in culture trigger the preferential expression of a tyrosinase isoenzyme different from the majority form found in untreated cells. Both forms differ in their electrophoretie mobility in non-reducing SDS-PAGE and in their catalytic properties. The isoenzyme preferentially induced by melanogenic agents displays a larger ratio of tyrosine hydroxylase to dopa oxidase activity, and would therefore mainly affect the first, rate limiting, step of the pathway. This finding conveniently accounts for most of the apparently controversial data in the literature. MATERIALS AND METHODS 2,1. Cell culture attd treatment with melanogenic effectorsBI6-F10 mouse melanoma cells were originally a kind gift of Dr. V. Hearing and have been maintained as described [8], BI6 melanocytes were culttared either on 96-well plates or in 75 cm: flasks from Nunc (Denmark). When using 9f-well plates, cells were seeded at a density of 5,000 ceils per well in 200/.tl of medium. After 24 h, serial dilutions of the melanogenie effectors were added in $0/,tl of medium, and the plate was further incubated for 48 h. Each concentration was assayed in six independent wells the contents of which were pooled by pairs before measurements so as to assay enzymatic activities in triplicate. To obtain higher amounts of cells for subcgllular fraetionation experiments. 5 • I0 S cells were sceclcd in 75 am" flasks, incubated for 24 h and then a volume of medium containing the desired con~ntra-lion of the melanogenic agent was added. Subcellular fractionattonCells were harvested by trypsin treatment and washed twice by centrifugation in homogenization buffer (HB, 10 mM phosphate pH 6.8, 0.25 M sucrose, 0.1 mM EDTA, 0.1 mM PMSF). The washed cells were suspended in HB at about I07 c.ll~'ml and disrupt,-d M a loosefitting, manual, glass-teflon homogenizer, at 4"C. A post-nuclear supernatant was obtained by centrifugation at 700 x g, and further 114Published by Elsevier Science Publishers B, K

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Section: I Introductionmentioning

confidence: 99%

Melanocyte stimulating hormone activation of tyrosinase in B16 mouse melanoma cells Evidence for a differential induction of two distinct isoenzymes

et al. 1992

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“…A variety of tyrosinase inhibitors of different chemical structure have been described (3). Moreover, modulations of the intracellular levels of such inhibitors have been postulated as a mechanism for tyrosinase regulation by extracellular messengers (54). Therefore we tested whether the inhibition mediated by TGF-␤1 could be accounted for by the induction of a tyrosinase inhibitor.…”

Section: Tgf-␤1 Inhibits Basal Melanogenesis In B16 Cellsmentioning

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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“…Wong and Pawelek, 1975;Halaban et al, 1983;Bennett, 1989;Haddad et al, 1999;Busca`and Ballotti, 2000). Pathways include both stimulation of transcription of specialized melanocytic proteins (for reviews, see Busca`and Ballotti, 2000;Goding, 2000) and post-translational activation of the key melanosomal enzyme tyrosinase (Wong and Pawelek, 1975). Human melanocytes approaching senescence show further increases in pigmentation and expression of some melanocytic proteins, even where already grown with cAMP agonists (Gilchrest et al, 1984;Medrano et al, 1994;Bennett et al, 1985;reviewed by Bennett and Medrano, 2002).…”

Section: Senescence In Cultured Human Melanocytesmentioning

confidence: 99%

“…Stimulation of pigment cell differentiation by cAMP agonists is a long-studied topic (e.g. Wong and Pawelek, 1975;Halaban et al, 1983;Bennett, 1989;Haddad et al, 1999;Busca`and Ballotti, 2000). Pathways include both stimulation of transcription of specialized melanocytic proteins (for reviews, see Busca`and Ballotti, 2000;Goding, 2000) and post-translational activation of the key melanosomal enzyme tyrosinase (Wong and Pawelek, 1975).…”

Section: Senescence In Cultured Human Melanocytesmentioning

confidence: 99%

Human melanocyte senescence and melanoma susceptibility genes

2003

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The molecular mechanisms and biology of cellular senescence in human melanocytes are discussed, including similarities to and differences from senescence in fibroblasts and other cell lineages. Special reference is made to the fact that the known melanoma susceptibility genes in the human, Inhibitor A of [cyclin-dependent] kinase 4-alternative reading frame (INK4A-ARF) and cyclindependent kinase 4, are involved in the regulation of cellular senescence, and possible reasons why this should be so. Based on the evidence including growth and survival kinetics of human and mouse melanocytes carrying germline deficiencies in the INK4A sequence, it is suggested that an 'M0' or p16/RB-dependent form of senescence may be particularly important in melanocytes. A speculative model is proposed, relating current concepts of early melanoma progression to the processes of cellular senescence and immortalization. This includes the suggestion that moles or nevi are senescent clones of melanocytes.

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Melanocyte-stimulating hormone promotes activation of pre-existing tyrosinase molecules in Cloudman S91 melanoma cells

Cited by 149 publications

References 6 publications

Melanocyte stimulating hormone activation of tyrosinase in B16 mouse melanoma cells Evidence for a differential induction of two distinct isoenzymes

Melanocyte stimulating hormone activation of tyrosinase in B16 mouse melanoma cells Evidence for a differential induction of two distinct isoenzymes

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

Human melanocyte senescence and melanoma susceptibility genes

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