Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.10.3.1 (tyrosinase)
 9,065 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

alpha-MSH (melanocyte-stimulating hormone) causes an increase in tyrosinase activity (O-diphenol-O2 oxidoreductase; EC 1.14.18.1) in Cloudman S-91 mouse melanoma cell cultures following a lag period of approximately 9 h. Treatment of cells with 2 X 10(-7)M alpha-MSH for 6 days results in a 90-fold increase in the specific activity of the enzyme. The hormone-mediated increase in tyrosinase activity is dependent upon continued transcription since the enzyme induction is suppressed by either cordycepin (1 microgram/ml) or alpha-amanitin (10 micrograms/ml). Immunoprecipitation analysis of pulse-labeled tyrosinase from control and MSH-treated cultures (48-h exposure) has demonstrated that MSH stimulates tyrosinase synthesis by approximately 4-fold, a level of induction which does not correspond to the observed 14-fold increase in enzyme activity. When immunotitration curves were developed from cell extracts of control and MSH-treated cultures using immunoprecipitation and competitive enzyme-linked immunosorbent assay protocols, evidence for the presence of immunologically active but catalytically less active enzyme in untreated melanoma cell cultures was demonstrated. Degradation rates of tyrosinase were found to be similar in control cultures or in cells treated with MSH for up to 48 h. Taken together, these results suggest that in addition to stimulating tyrosinase synthesis, MSH may also promote an increase in the catalytic efficiency of the enzyme.
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PMID:Alpha-melanocyte-stimulating hormone regulation of tyrosinase in Cloudman S-91 mouse melanoma cell cultures. 303 Oct 58

Bromocriptine, a dopamine agonist that blocks the secretion of MSH, inhibits melanogenesis in the hair follicular melanocytes of pubertal C3H-HeAvy mice. However, since this effect cannot be explained by a reduction in circulating alpha-MSH, we have examined the possibility that dopaminergic mechanisms may have a direct inhibitory effect on these melanocytes. Bromocriptine decreased tyrosinase activity in skin explants from 30- to 35-day-old mice that were growing dark hair. This decrease in tyrosinase activity was blocked by dopamine receptor antagonists, haloperidol or spiperone. The specific D2 agonist LY 171555 also inhibited tyrosinase activity in the skin explants in a dose-related manner and the effect was blocked by sulpiride, a D2-receptor antagonist. Neither bromocriptine nor LY 171555 had any effect on tyrosinase activity in skin explants taken from adult mice that were growing yellow hair. The D1-receptor agonist SKF 38393 had no effect on tyrosinase activity in skin explants from either group of mice. The present results support the idea that dopamine D2-receptor agonists have a direct inhibitory effect upon tyrosinase activity of hair follicular melanocytes of the C3H-HeAvy mouse. However, this effect was confined to periods of dark hair growth when the melanocytes produce eumelanin. The D2 agonists were ineffective in reducing tyrosinase activity during adult life when the melanocytes produce predominantly phaeomelanin. This suggests that different control mechanisms may operate in the hair follicular melanocytes during periods of eumelanin and phaeomelanin synthesis.
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PMID:Dopaminergic inhibition of tyrosinase activity in hair follicular melanocytes of the mouse. 309 85

Bomirski Ab amelanotic melanoma cells have recently been shown to undergo striking phenotypic changes when precursors of the melanogenic pathway, L-tyrosine and L-dopa, are added to the culture medium. The changes include increased tyrosinase activity and de novo synthesis of melanosomes and melanin. L-tyrosine and L-dopa appeared to elicit these responses through separate but overlapping regulatory pathways. Here we show an additional effect of L-tyrosine: stimulation of MSH binding capacity. Cells cultured for 24-48 hours in the presence of 200 microM L-tyrosine display a 3-4 fold increase in their ability to bind 125I-beta-MSH. L-dopa did not stimulate MSH binding under the same conditions. In control experiments neither L-tyrosine nor L-dopa had any effect on insulin binding. The amelanotic cells respond to MSH with increased dendrite formation, increased tyrosinase activity without melanin production, and decreased growth rate.
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PMID:MSH binding in Bomirski amelanotic hamster melanoma cells is stimulated by L-tyrosine. 313 59

Cloudman S91 mouse melanoma cells respond in culture to B-melanocyte-stimulating hormone (B-MSH) with changes in morphology, growth rates, and melanin production. The effects of MSH appear to be mediated through a stimulation of the cyclic AMP system. It was reported earlier that at least some of the responses to MSH (increased cyclic AMP production and tyrosinase activity) occur in the G2 phase of the cell cycle [Wong, G., Pawelek, J., Sansone, M., & Morowitz, J. (1974) Nature (London) 248, 351-354] and that the apparent reason for this cell cycle restriction is that receptors for MSH are most active in the G2 phase [Varga, J. M., DiPasquale, A., Pawelek, J., McGuire, J., & Lerner, A. (1974) Proc. Natl. Acad. Sci. U.S.A. 71, 1590-1593]. In this report, we found that by two separate methods of obtaining populations of cells in the G2 phase of their cycle--centrifugal elutriation or synchronization with thymidine--we observed increased binding of MSH by cells in the G2 and possibly late S phases of their cycle. However, cultures of cells passing through their cycle in synchrony were quite different from nonsynchronized (random) cultures. Both synchronized and random cultures expressed receptors for MSH in the G2 and possibly late S phases of their cycle, but synchronized cultures bound severalfold more MSH per cell than random cultures. This increased binding of MSH by synchronized cells was accompanied by an increase in tyrosinase activity and pigment production.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Receptors for B-melanocyte-stimulating hormone exhibit positive cooperativity in synchronized melanoma cells. 313 2

Cloudman S91 mouse melanoma cells lose their ability to demonstrate an MSH-induced increase in tyrosinase activity as cell density increases. This loss in hormone responsiveness occurs before confluency is reached and cannot be reversed by exposure of cells to increasing concentrations of MSH. The failure of high-density cultures to respond to MSH is apparently not the result of an inability of MSH to stimulate cAMP production, since either low- or high-density cultures exposed to MSH demonstrate equivalent increases in intracellular levels of cAMP. Further, neither theophylline (1mM), dibutyryl cyclic AMP (10(-4)M), or prostaglandin E1 (10(-6)M) is effective in stimulating tyrosinase activity in melanoma cells cultured at densities exceeding 6 X 10(4) cells/cm2. This finding suggests that the decay of hormone responsiveness occurs at a cellular site distal to cAMP production. The decrease in tyrosinase stimulation by MSH as cell density increases is also apparently not the result of an increase in activity of any soluble inhibitor of the enzyme, for cytosol preparations from high-density cultures (10(5) cells/cm2) fail to inhibit tyrosinase activity in cell homogenates from low-density cultures treated with MSH.
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PMID:Decay of hormone responsiveness in mouse melanoma cells in culture as a function of cell density. 625 96

Studies were performed for the investigation of endocrine responsiveness in cell lines derived from either normal human melanocytes or human melanoma cells. Alterations in differentiation (tyrosinase activity) were determined in cells exposed to either melanocyte-stimulating hormone (MSH, 10(-7) M), theophylline (10(-3) M), N6,O2'-dibutyryl cyclic AMP (db-cAMP, 10(-4) M), or prostaglandin E1 (PGE1, 10(-6) M). Cultures derived from normal uveal melanocytes demonstrated increased tyrosinase activity upon exposure to either theophylline, db-cAMP, or PGE1, but not to MSH. However, MSH responsiveness was detected in 7 of 11 human melanoma cell lines. Four cell lines demonstrated increased activity of tyrosinase after MSH treatment, whereas three lines showed an MSH-induced inhibition of enzyme activity. PGE1 was effective in stimulating tyrosinase activity in five of nine cell lines examined. Theophylline was the most effective stimulator of tyrosinase in melanoma-derived cell populations and caused increased enzyme activity in eight of eleven cell lines.
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PMID:Endocrine responsiveness in human melanocytes and melanoma cells in culture. 626 56

In short-term (48 h) cultures of hair follicles alpha-melanocyte-stimulating hormone (alpha-MSH) and cyclic AMP stimulated melanogenesis through an increase in tyrosinase activity. In contrast cyclic GMP mimicked the effects of melatonin by inhibiting melanin production without causing a concomitant decrease in tyrosinase activity. Both cyclic GMP and melatonin blocked the stimulatory effects of cyclic AMP and alpha-MSH on melanin production but they left the increased levels of tyrosinase activity unaffected. Phosphodiesterase inhibitors (3-isobutyl-1--methylxanthine and papaverine) simultaneously stimulated tyrosinase activity and inhibited melanin production, presumably by allowing endogenous cyclic AMP and cyclic GMP to accumulate intracellularly. It is suggested that whereas MSH stimulates melanogenesis through a cyclic AMP-dependent mechanism there must also be an inhibitory cyclic GMP-dependent mechanism, perhaps activated by melatonin, which operates at some post-tyrosinase step in the melanin biosynthetic pathway.
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PMID:Interaction of alpha-melanocyte-stimulating hormone, melatonin, cyclic AMP and cyclic GMP in the control of melanogenesis in hair follicle melanocytes in vitro. 626 54

Melanocyte-stimulating hormone (alpha-melanotropin, MSH) may function in a number of diverse physiological roles. MSH stimulates (1) rapid translocation of melanosomes (melanin granules) in dermal melanophores to effect rapid colour change and (2) melanogenesis in normal and abnormal (melanoma) epidermal melanocytes. Both actions involve (1) initial binding of the peptide on the melanocyte membrane, (2) transduction of signal to adenylate cyclase, and (3) increased cytosolic levels of cyclic AMP. Efforts to prepare radioiodinated MSH and analogues for radioreceptor studies using melanoma membranes and intact cells reveal that conventional iodination procedures inactivate the hormone because of oxidative and iodination effects on specific structural components of the peptide. These effects can be circumvented by the use of synthetically tailored MSH analogues. Transduction of signal from receptor to adenylate cyclase requires calcium, but prostaglandin or beta-adrenoceptor stimulation of melanophores does not. The nucleotide and metal ion requirements for mouse melanoma adenylate cyclase activity have been characterized. There is both a transcriptional and translational requirement for MSH stimulation of tyrosinase activity and melanin production in melanoma cells. Melanosome translocation within melanophores is enhanced in the absence of extracellular calcium. A model for the MSH control of melanosome movements suggests a bifunctional, but compartmentalized, role for calcium in the action of MSH.
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PMID:Biological actions of melanocyte-stimulating hormone. 626 80

alpha-Melanocyte-stimulating hormone (alpha-MSH) has been shown to act directly on the mammalian melanocyte in short-term cultures of hair follicles obtained from the Siberian hamster. Melanogenesis was stimulated through an increase in tyrosinase activity which resulted in an increase in melanin production. The response of hair follicle melanocytes to alpha-MSH occurred only in follicles taken from moulting animals, implying that they show a discontinuous expression of MSH receptors during the hair follicle growth cycle. Synthetic 1-24 ACTH had no effect on melanogenesis regardless of whether the follicles came from moulting or non-moulting animals. The pineal peptide, [8-arginine]-vasotocin (AVT), inhibited melanin production without a concomitant decrease in tyrosinase activity. In this respect AVT resembled melatonin, although AVT showed a potency ratio of less than half on a molar basis. The action of AVT, like that of melatonin, must ultimately be on some post-tyrosinase step in melanin biosynthesis. In these hair follicle melanocytes AVT seems to bind to specific receptors since neither of the closely related peptides, oxytocin and [8-arginine]-vasopressin, displayed any activity in our culture system.
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PMID:Effects of alpha-melanocyte-stimulating hormone and [8-arginine]-vasotocin upon melanogenesis in hair follicle melanocytes in vitro. 627 86

Insulin lowers basal levels of tyrosinase activity and inhibits the MSH-induced increase in tyrosinase in Cloudman S-91 mouse melanoma cell cultures. Insulin exerts its inhibitory effects in a typical dose-response manner, with maximal inhibition of enzyme activity occurring at 10-7 M. At maximal inhibition, tyrosinase activity is reduced to approximately 50% of the control levels. This inhibition precedes the observed inhibitory effect on cellular proliferation. Insulin not only lowers cell responsiveness to MSH, but also inhibits the tyrosinase stimulation produced by either theophylline or (Bu)2cAMP. Neither control levels nor MSH-mediated elevated cellular levels of cAMP were altered by insulin (10-7 M). These findings suggest that insulin exerts its inhibitory effects at a site distal to cAMP production. The inhibitory effect of insulin on tyrosinase activity could not be mimicked by either (Bu)2cGMP or 8-bromo-cGMP, suggesting that insulin does not exert its effects by altering cellular levels of this nucleotide. Insulin reduces the rate of incorporation of [3H]leucine into trichloroacetic acid-precipitable material by 50%, a finding which suggests that insulin may exert its inhibitory effects on tyrosinase activity and perhaps on cellular proliferation by causing a general reduction in protein synthetic rates.
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PMID:Insulin-mediated inhibition of tyrosinase activity and protein synthesis in melanoma cell cultures. 631 45


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