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

Human melanocytes, maintained on bovine corneal endothelium-derived extracellular matrix for at least 4 days in the absence of phorbol 12-myristate 13-acetate (PMA) and cholera toxin (CT), displayed increased tyrosinase activity when exposed to several pro-opiomelanocortin-derived (POMC) peptides. Melanocytes from 9 of 14 donors showed significantly increased tyrosinase activity after treatment with adrenocorticotropic hormone (ACTH; mean increase 320 +/- 107 (S.E.M.)% of control, P < 0.005), while melanocytes from 8 of 13 donors increased tyrosinase in the presence of diacetyl-melanocyte stimulating hormone (di-MSH; mean increase 223 +/- 31 (S.E.M.)% of control, P < 0.005). Maximal increases in tyrosinase were seen after treatment with 10(-10) M ACTH and with 10(-6) M di-MSH. In two cell cultures which showed tyrosinase stimulation, melanin synthesis was similarly increased in the presence of added POMC peptides. PMA but not CT increased tyrosinase activity in melanocytes cultured under these conditions. In the presence of staurosporine, an inhibitor of protein kinase C (PKC), the magnitude of the increase in tyrosinase due to PMA, ACTH and di-MSH was significantly reduced. These results indicate that tyrosinase activity in melanocytes from most human donors, under appropriate conditions, is susceptible to the stimulatory effects of POMC peptides, that ACTH is considerably more potent than di-MSH in this test system and that in human cells the PKC pathway may be important in modulating melanogenesis.
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PMID:Stimulation of tyrosinase in human melanocytes by pro-opiomelanocortin-derived peptides. 759 39

The significance of melanotropic hormones as physiologic regulators of cutaneous pigmentation in humans is still controversial. Until recently, no direct effect for melanotropins could be demonstrated on human melanocytes. Here we present conclusive evidence that alpha-melanotropin (alpha-melanocyte-stimulating hormone, alpha-MSH) and the related hormone corticotropin (adrenocorticotropic hormone, ACTH) stimulate the proliferation and melanogenesis of human melanocytes maintained in culture in a growth medium lacking any AMP inducer. The minimal effective dose of either hormone is 0.1 nM. In time-course experiments, the increase in cell number and tyrosinase activity became evident after one treatment of the melanocytes with 100 nM alpha-MSH for 48 hr. The mitogenic effect gradually increased to 50-270% above control, depending on the individual melanocyte strain, with continuous treatment with 100 nM alpha-MSH for 8 days, whereas the melanogenic effect became maximal (70-450% increase above control) after 4 days of treatment. Western blot analysis of tyrosinase and the tyrosinase-related proteins TRP-1 and TRP-2 revealed that alpha-MSH increased the expression of those three melanogenic proteins. This was not accompanied by any change in their mRNA levels after brief (1.5-24 hr) or prolonged (6 days) treatment with 100 nM alpha-MSH, suggesting that the increased expression of these melanogenic proteins was due to posttranscriptional events. These results demonstrate both mitogenic and melanogenic effects of alpha-MSH and ACTH on human melanocytes. That both hormones are effective at subnanomolar concentrations, combined with the presence of melanotropin receptors on human melanocytes, strongly suggests that these melanotropins play a physiologic role in regulating human cutaneous pigmentation.
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PMID:Mitogenic and melanogenic stimulation of normal human melanocytes by melanotropic peptides. 787 59

Compelling evidence suggest a role for melanocortins in the regulation of melanogenesis by ultraviolet radiation. Within the epidermis, melanocytes and keratinocytes produce alpha-melanocyte-stimulating hormone and adrenocorticotropic hormone. The persistence and the strength of the biologic signal delivered by these peptides depend on their local concentration, which is controlled by the rate of peptide production and by the rate of its degradation. In this study, we investigated the mechanism of melanocortin degradation by melanocytes and the effect of ultraviolet on this process. We have focused our attention on a neutral endopeptidase, neprilysin, which has been implicated in the ending of numerous peptidergic signals. We have shown that this enzyme is expressed at the surface of human melanocytes. Interestingly, its activity and its expression are dramatically downregulated by ultraviolet B treatment. Moreover, in the presence of phosphoramidon, a stable inhibitor of neprilysin, we observed an increased efficiency of alpha-melanocyte-stimulating hormone and adrenocorticotropic hormone to stimulate both tyrosinase activity and microphthalmia expression. Taken together, these data indicate that neprilysin expressed by melanocytes has a physiologic role in the regulation of melanogenesis by proopiomelanocortin peptide. Further, its downregulation by ultraviolet B irradiation shed light on a new and appealing mechanism of ultraviolet B induced melanogenesis via the control of melanocortins degradation.
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PMID:Neprilysin, a novel target for ultraviolet B regulation of melanogenesis via melanocortins. 1095 Dec 72

In ultraviolet-induced tanning, the protein levels of various gene products critical for pigmentation (including tyrosinase and tyrosinase-related protein-1) are increased in response to ultraviolet B irradiation, but changes in mRNA levels of these factors have not been investigated in vivo. We have established an in situ hybridization technique to investigate mRNA levels of pro-opiomelanocortin, tyrosinase, tyrosinase-related protein-1, dopachrome tautomerase, P-protein, Pmel-17/gp100, and microphthalmia-associated transcription factor, and have analyzed the changes in mRNA levels in the ultraviolet B-exposed skin in vivo. The right or left forearm of each volunteer was irradiated with ultraviolet B, and skin biopsies were obtained at 2 and 5 d postirradiation. mRNA level of pro- opiomelanocortin was increased 2 d after ultraviolet B irradiation, and returned to a near-basal level after 5 d, whereas the mRNA levels of tyrosinase, tyrosinase-related protein-1, dopachrome tautomerase, P-protein, and Pmel-17/gp100 showed some or no increase at 2 d, but were significantly increased 5 d after ultraviolet B irradiation. Microphthalmia-associated transcription factor mRNA was slightly increased on days 2 and 5 after ultraviolet B irradiation. Our results suggest that the mechanism of the tanning response of human skin may involve the transcriptional regulation of certain pigmentary genes, and that pro-opiomelanocortin-derived melanocortins such as alpha-melanocyte-stimulating hormone and adrenocorticotropic hormone may play a part in regulating these genes in vivo.
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PMID:Increase of pro-opiomelanocortin mRNA prior to tyrosinase, tyrosinase-related protein 1, dopachrome tautomerase, Pmel-17/gp100, and P-protein mRNA in human skin after ultraviolet B irradiation. 1185 78

It was reported that adrenocorticotropic hormone stimulates melanogenesis in cultured melanocytes. Stress (high population density and restraint stress) induced a significant increase in adrenocorticotropic hormone levels in plasma and skin compared to control. The serum obtained from HR-1 x HR/De F1 female mice subjected to stress showed significantly increased tyrosinase activity in human melanocytes compared to that from nonstressed mice. The increase in tyrosinase activity was inhibited in the presence of 10 nM corticostatin, an adrenocorticotropic hormone inhibitor. The aim of this study was to examine whether adrenocorticotropic hormone released into the circulation under stressful conditions is associated with the regulation of ultraviolet-induced pigmentation. Mice divided into three groups were housed for 22 d under the following conditions: five mice per cage (control); 10 mice per cage (high population density); restraint stress 4 h per d. The animals were exposed to ultraviolet-B irradiation (72 mJ per cm2, thrice per wk). After ultraviolet-B irradiation, delayed tanning was marked in stressed mice. The number of dihydroxyphenylalanine-positive melanocytes also significantly increased in stressed animals. Pretreatment with 100 microg of corticostatin inhibited the augmentation of the stress-induced pigmentary response and the increase in dihydroxyphenylalanine-positive melanocytes after ultraviolet irradiation. Adrenocorticotropic hormone released by stress may activate tyrosinase in melanocytes, resulting in the augmentation of ultraviolet-induced pigmentation. These results suggest that adrenocorticotropic hormone is at least partly responsible for the sensitivity of the pigmentary response after ultraviolet irradiation under stressful conditions.
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PMID:Stress augmented ultraviolet-irradiation-induced pigmentation. 1283 77