Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01189 (beta-endorphin)
 21,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A variant of B-16 F1 mouse melanoma was selected for its ability to survive and replicate in the presence of melanocyte-stimulating hormone (MSH). Although the variant (MR-4) was completely resistant to growth inhibition of MSH, cyclic AMP was still able to block cell replication. Tyrosinase activity in MR-4 cells was considerably lower than in B-16 F1 cells. MSH induced a two fold to three-fold increase in tyrosinase activity in both cell types, but the absolute activity in MR-4 remained significantly less than in the parental cells. MR-4 cells were also found to have a markedly depressed cyclic AMP-dependent protein kinase activity relative to B-16 F1 cells. The protein kinase from both cell types was stimulated by cyclic AMP, but the level of MR-4 kinase activity at maximal cyclic AMP concentrations remained considerably lower than B-16 F1 kinase activity under the same conditions. In both cell types adenylate cyclase activity was markedly stimulated by MSH. When equal numbers of viable F1 and MR-4 cells were injected subcutaneously into C57/B1 mice, the MR-4 cells formed tumors earlier and killed the host sooner than the parental F1 cells. We conclude that the biochemical alteration which allows MR-4 cells to replicate in the presence of MSH is a low level of tyrosinase activity, which in turn may be the result of low cyclic AMP-dependent protein kinase activity.
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PMID:Isolation and characterization of a variant of B16-mouse melanoma resistant to MSH growth inhibition. 23 92

Mouse melanoma cells in culture respond to melanocyte-stimulating hormone (MSH) or to cyclic AMP analogues by demonstrating an increase in tyrosinase activity. In this study the effect of the tumor promoter, 12-O-tetradecanoylphorbol 13-acetate (TPA), on the hormonal induction of tyrosinase was examined. TPA was found to lower basal levels of tyrosinase activity in melanoma cells and to reduce tyrosinase levels in cells treated with either MSH (10(-7) M), dibutyryl cAMP (10(-4) M), isobutylmethylxanthine (IBMX, 10(-4) M), or with the potent MSH analogue, [Nle4,D-phe7]-alpha-MSH. The phorbol ester, phorbol 12,13-dibutyrate was also effective in lowering tyrosinase activity levels, while 4 alpha-phorbol 12,13-didecanoate, which does not bind protein kinase C, was ineffective. In order to determine how TPA may reduce tyrosinase activity in melanoma cells, the levels of tyrosinase mRNA in untreated or TPA-treated cells were determined by Northern blot analysis. A marked down-regulation of constitutive levels of tyrosinase mRNA was observed in cells treated with the tumor promoter. Tyrosinase mRNA levels in cultures exposed to TPA for 48 h were only 7% of control levels. Tyrosinase mRNA levels in cells treated with both MSH and TPA were also lower than in cells treated with MSH alone. Previous studies from this laboratory have shown that insulin both lowers basal tyrosinase activity in melanoma cells and antagonizes the MSH stimulation of the enzyme. We have now determined that this inhibition is also due to reduced levels of tyrosinase mRNA.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Down-regulation of tyrosinase mRNA levels in melanoma cells by tumor promoters and by insulin. 170 21

A human foreskin organ culture system has been developed to study the response of human skin to hormonal stimulation. Foreskins are maintained in culture on floating plastic supports which allows the epidermal surface to be exposed to air while the dermis is bathed in nutrient medium. Both black and white human foreskins can be maintained in organ culture for at least 1 wk with no change in the tissue structure or cell viability as determined by histochemical staining and by dopa reaction staining. Tyrosinase activity in both black and white human foreskin cultures decays markedly during the first 2 d of culture to a new steady state level which remains stable throughout the culture period. Both black and white foreskin cultures consistently demonstrate 2- to 10-fold increases in tyrosinase activity when treated with theophylline (1 mM). Approximately 90% of all skin cultures examined showed an increase in enzyme activity when treated with this phosphodiesterase inhibitor. Dibutyryl cAMP (0.1 mM) and [Nle4, D-phe7]-alpha MSH (10(-8) M), were also found to markedly stimulate tyrosinase activity in some skin cultures, whereas alpha-MSH and prostaglandin E1 produced only an inconsistent and small increase in the activity of the enzyme. Histamine (1 microM), vitamin D3 (1 microM), and retinoic acid (1 microM) failed to stimulate tyrosinase activity in either white or black foreskin cultures. This hormone-responsive organ culture system can be utilized to characterize the molecular processes responsible for the regulation of tyrosinase and pigmentation in human skin.
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PMID:Hormonal stimulation of tyrosinase activity in human foreskin organ cultures. 216 16

Tyrosinase synthesis and its regulation in human melanocytes was studied by measuring the incorporation of [35S] methionine into incubated skin biopsies. Tyrosinase was detected in all skin samples with the highest levels in skin type IV and the lowest levels in skin type I. Following psoralen ultraviolet A (PUVA) therapy for several weeks, significant increases in the amounts of tyrosinase were found in skin types III and IV. The presence of alpha-melanocyte-stimulating hormone (alpha-MSH) (100 mumol/l) or the long-acting analogue [Nle4, DPhe7] alpha-MSH (1-10 mumol/l) in the incubation medium failed to alter tyrosinase levels in the skin biopsies taken from patients both before and after receiving PUVA therapy. Bromo-adenosine 3,5-cyclic monophosphate sodium salt (8-bromo-cAMP) (10 mmol/l), on the other hand, increased the amounts of tyrosinase both before and after PUVA, but these effects were only seen in biopsies of type III and IV skin. These results indicate that MSH fails to stimulate tyrosinase synthesis in human melanocytes. Nevertheless, tyrosinase synthesis and its regulation by cyclic AMP-dependent mechanisms could be important control points in the pigmentary response.
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PMID:Tyrosinase synthesis in different skin types and the effects of alpha-melanocyte-stimulating hormone and cyclic AMP. 217 91

Mouse melanoma cells in culture respond to melanocyte-stimulating hormone (MSH) by demonstrating increased activity of tyrosinase, the rate-limiting enzyme for melanin synthesis. Because this stimulation is strictly dependent upon continued transcription and translation, we have carried out studies to determine if MSH increases the level of tyrosinase mRNA. The abundance of tyrosinase message levels in melanoma cells treated with either MSH or dibutyryl cAMP was determined by Northern blot analysis utilizing a 946 base pair mouse tyrosinase cDNA probe. The tyrosinase cDNA was isolated from a lambda gt11 expression library generated from mRNA isolated from theophylline-induced Cloudman melanoma cells. The abundance of tyrosinase mRNA was determined in an amelanotic cell clone (AM-7AS) and a melanotic cell clone (MEL-11AS). The melanotic cell line had five times as much tyrosinase activity and almost 10 times more tyrosinase mRNA than the amelanotic line. Tyrosinase activity and mRNA increased in both cell lines after MSH addition. The amelanotic line treated with MSH for three days showed a fivefold increase in tyrosinase activity and a twofold increase in tyrosinase mRNA. The melanotic cell line treated with MSH for three days showed a 3.7-fold increase in enzyme activity and an eightfold increase in the abundance of tyrosinase mRNA. Dibutyryl cAMP also stimulated tyrosinase activity and the accumulation of tyrosinase mRNA. The data suggest that MSH, acting through cAMP, promotes an accumulation of tyrosinase mRNA.
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PMID:Regulation of tyrosinase mRNA levels in mouse melanoma cell clones by melanocyte-stimulating hormone and cyclic AMP. 254 86

In Bomirski Ab amelanotic hamster melanoma cells, L-tyrosine and/or L-dopa induce increases in tyrosinase activity as well as synthesis of melanosomes and melanin. L-tyrosine also modifies melanocyte-stimulating hormone (MSH) binding. In this paper we show that in the Bomirski amelanotic melanoma system MSH and agents that raise intracellular cyclic AMP induce dendrite formation, inhibit cell growth, and cause substantial increases in tyrosinase activity without inducing melanin synthesis. Tyrosinase activity is detected only in broken cell preparations, or cytochemically in fixed cells. In the continued absence of mature melanosomes, the induced enzyme remains in elements of the trans-Golgi reticulum. Comparative measurements of cyclic AMP in amelanotic and tyrosine-induced melanotic cells show similar basal levels. L-tyrosine and L-dopa have little or no effect, whereas MSH may cause a 1000% peak increase in cyclic AMP levels both in amelanotic and melanotic cells. None of these agents influences cyclic GMP or inositol trisphosphate (InsP3) levels. In agreement with the InsP3 assays, phorbol ester (TPA) has no effect on melanization, tyrosinase activity or cell proliferation. In conclusion, in the Bomirski amelanotic melanoma, MSH induces only partial cell differentiation associated with raised levels of cyclic AMP. Induction of melanosome synthesis and melanization by L-tyrosine or L-dopa appear to follow pathways unrelated to cyclic AMP, cyclic GMP or InsP3.
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PMID:MSH inhibits growth in a line of amelanotic hamster melanoma cells and induces increases in cyclic AMP levels and tyrosinase activity without inducing melanogenesis. 255 57

Tyrosinase activity was increased in hair follicular melanocytes of C3H-HeAvy mice during the hair cycle and reached higher levels on days 6-8 after plucking than on day 12. Similarly, the rate of incorporation of [35S]methionine into tyrosinase was greater on days 6-8 than on day 12, but the relative difference was much less. alpha-MSH had no effect on tyrosinase activity or the rate of [35S]methionine incorporation on day 12 and, while it increased both on days 6 and 8, it had a greater effect upon the latter. Pulse-chase experiments showed that the half-life of tyrosinase was 3.5 h and that this was unaffected by alpha-MSH. The results indicate that the increases in tyrosinase activity which occur during the hair cycle involve changes in both the synthesis and activation of the enzyme and that the predominant effect of alpha-MSH is on the former of these two processes.
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PMID:Regulation of tyrosinase synthesis by alpha-melanocyte-stimulating hormone in hair follicular melanocytes of the mouse. 282 5

Dopachrome oxidoreductase (DCOR) is a newly characterized enzyme in the melanin synthetic pathway, active in the conversion of dopachrome to 5,6-dihydroxyindole. DCOR and tyrosinase activity were measured in skin anagen hairbulbs from lethal yellow (Ay/a), sienna yellow (Asy/a) and recessive yellow (e/e) mice with and without treatment with melanocyte-stimulating hormone (MSH). DCOR activity was low (Asy/a) or absent (Ay/a, e/e) in yellow mice without MSH treatment, and increased dramatically in the lethal and sienna yellow mice with MSH. There was no increase in DCOR activity in recessive yellow mice with MSH. Corresponding tyrosinase activity was reduced in lethal yellow and sienna yellow mice without MSH, and increased with MSH. Tyrosinase activity was normal in recessive yellow mice without MSH and did not change with MSH. We conclude that DCOR is an MSH-sensitive enzyme and that DCOR activity is absent in recessive yellow melanocytes. The latter finding suggests that the extension locus may be the DCOR locus.
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PMID:Decreased dopachrome oxidoreductase activity in yellow mice. 392 Mar 5

The influence of single amino acid replacements by alanine on the binding affinity and biological activity of alpha-MSH in B16 murine melanoma cells has been studied systematically. alpha-MSH analogues were synthesized by solid-phase peptide synthesis and their binding affinities to the melanocortin receptor expressed by B16 mouse melanoma cells were determined using a radioreceptor assay. Biological activity of the analogues was determined by measuring tyrosinase stimulation. Relative activity and affinity data were generally in agreement with earlier results using terminal deletion fragments of alpha-MSH, but the alanine scan revealed important new insights into the role of individual residues. The three terminal amino acids at either end were not necessary for binding or activity, with amino acids 4-9 forming a core sequence required for receptor binding and triggering of the biological response. It was observed that replacement of the glutamic acid residue in position 5 was possible without loss of affinity or activity, whereas replacement of Met4 resulted in a 100-fold loss of binding affinity and biological activity. Each residue within the conserved melanocortin sequence His-Phe-Arg-Trp was shown to be essential with Phe7, Arg8, and Trp9 being the most sensitive to replacement by alanine. Generally, there was a rank correlation between binding affinity and tyrosinase stimulation within the group of analogues studied. Tyrosinase activity was less affected by alanine substitution than binding affinity, which suggests that full receptor binding is not required for maximum biological response.
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PMID:Synthesis and biological evaluation of alpha-MSH analogues substituted with alanine. 785 84

Using antibodies that recognize either tyrosinase, tyrosinase-related protein-1 (TRP1), or tyrosinase-related protein-2 (TRP2, DOPAchrome tautomerase), the quantities of those melanogenic enzymes were analyzed in five melanoma cell lines that possess various degrees of melanin production. All cells except JB/MS-W increased melanin production four to 30 times after 4 d of melanocyte-stimulating hormone (MSH) treatment. Melanin production by JB/MS-W cells was always under background, with or without MSH treatment. There was a positive correlation between quantities and synthetic rates of those melanogenic enzymes and their melanin formation or DOPAchrome tautomerase activities. The activity of a heat-resistant melanogenic inhibitory factor was also analyzed. The results showed, surprisingly, that pigmented cells showed higher levels of melanogenic inhibitors activity. Tyrosinase activity was increased dramatically whereas the level of melanogenic inhibitor was remarkably decreased following MSH treatment. Interestingly, melanogenic inhibitor derived from JB/MS-W cells suppressed not only tyrosinase but also DOPAchrome tautomerase, another enzyme functional in melanin production. These results clearly suggest that melanin production is regulated by a subtle balance between the activities of these enzymes and other factors such as the melanogenic inhibitor.
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PMID:Pigment production in murine melanoma cells is regulated by tyrosinase, tyrosinase-related protein 1 (TRP1), DOPAchrome tautomerase (TRP2), and a melanogenic inhibitor. 842 35


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