Repeated UVB irradiations do not have the same potential to promote stimulation of melanogenesis in cultured normal human melanocytes

1993 ◽  
Vol 106 (4) ◽  
pp. 1015-1022 ◽  
Author(s):  
E. Aberdam ◽  
C. Romero ◽  
J.P. Ortonne

The major stimulus for human melanin production is ultraviolet (UV) radiation. Little is known about the mechanisms underlying this response and the eventual enzyme regulation resulting from this activation. We treated normal human melanocytes in culture with daily UVB radiations. Cumulative increases in UVB doses resulted in proportional increases in tyrosinase activity over the first few days whereas an intermittent pattern of tyrosinase activation was observed after the fifth day of irradiation. This intermittent pattern consisted of latency periods where no melanogenic response was elicited despite exposure to UVB. Tyrosinase activity in cellular extracts increased shortly after an effective irradiation, peaked at 3 hours and thereafter decreased to below basal levels. Increased tyrosinase activity was associated with increased amounts of both the newly synthesized and mature forms of the enzyme. Decreased tyrosinase activity following an activation period was correlated with decreases in both the expression of tyrosinase mRNA and the amount of the newly synthesized form of the enzyme present in the melanocytes 24 hours after six irradiations. This particular pattern of stimulation of tyrosinase was not observed in S-91 murine melanoma cells after repeated UVB irradiations. Taken together these results may suggest a photo-protective mechanism developed by irradiated normal human melanocytes.

Cosmetics ◽  
2020 ◽  
Vol 7 (3) ◽  
pp. 55
Author(s):  
Yoshihiro Tokudome ◽  
Tsuyoshi Hoshi ◽  
Sayaka Mori ◽  
Ichiro Hijikuro

Several resorcinol derivatives were synthesized and their effects on the survival rate of B16 murine melanoma cells, melanin production, and tyrosinase activity were investigated with an aim to evaluate their skin whitening effect. Twelve resorcinol derivatives were synthesized by esterification with three functional groups (L-ascorb-6-yl, ethyl, and glyceryl) linked via four alkyl chains of varying lengths (n = 2–5) at the 4-position. The structures of the 12 resorcinol derivatives were confirmed by Nuclear Magnetic Resonance (NMR). The derivatives were added to B16 murine melanoma cells and the melanin contents in the cells and culture medium were measured. To measure the tyrosinase activity, the substrate L-DOPA was added to a mushroom-derived tyrosinase solution, and the inhibition of the tyrosinase activity was determined. At 10 µM, the resorcinol derivatives did not affect the survival of the B16 murine melanoma cells, but the melanin content was reduced. At 1 µM, the derivatives significantly inhibited the tyrosinase activity in the mushroom-derived tyrosinase solution. A plot of the inhibitory effect on melanin production against the cLogP value for each resorcinol derivative indicated that the highest inhibition occurred at a cLogP value of approximately 2. Therefore, these resorcinol derivatives are expected to serve as effective skin whitening agents.


2021 ◽  
Vol 22 (7) ◽  
pp. 3755
Author(s):  
Jakub Rok ◽  
Zuzanna Rzepka ◽  
Justyna Kowalska ◽  
Klaudia Banach ◽  
Artur Beberok ◽  
...  

Minocycline is a drug which induces skin hyperpigmentation. Its frequency reaches up to 50% of treated patients. The adverse effect diminishes the great therapeutic potential of minocycline, including antibacterial, neuroprotective, anti-inflammatory and anti-cancer actions. It is supposed that an elevated melanin level and drug accumulation in melanin-containing cells are related to skin hyperpigmentation. This study aimed to evaluate molecular and biochemical mechanism of minocycline-induced hyperpigmentation in human normal melanocytes, as well as the contribution of UV radiation to this side effect. The experiments involved the evaluation of cyto- and phototoxic potential of the drug using cell imaging with light and confocal microscopes as well as biochemical and molecular analysis of melanogenesis. We showed that minocycline induced melanin synthesis in epidermal melanocytes. The action was intensified by UV irradiation, especially with the UVB spectrum. Minocycline stimulated the expression of microphthalmia-associated transcription factor (MITF) and tyrosinase (TYR) gene. Higher levels of melanin and increased activity of tyrosinase were also observed in treated cells. Moreover, minocycline triggered the supranuclear accumulation of tyrosinase, similar to UV radiation. The decreased level of premelanosome protein PMEL17 observed in all minocycline-treated cultures suggests disorder of the formation, maturation or distribution of melanosomes. The study revealed that minocycline itself was able to enhance melanin synthesis. The action was intensified by irradiation, especially with the UVB spectrum. Demonstrated results confirmed the potential role of melanin and UV radiation minocycline-induced skin hyperpigmentation.


1995 ◽  
Vol 146 (3) ◽  
pp. 439-447 ◽  
Author(s):  
S D McLeod ◽  
C Smith ◽  
R S Mason

Abstract 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-opiomelanocortinderived (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. Journal of Endocrinology (1995) 146, 439–447


1995 ◽  
Vol 92 (5) ◽  
pp. 1789-1793 ◽  
Author(s):  
Z. Abdel-Malek ◽  
V. B. Swope ◽  
I. Suzuki ◽  
C. Akcali ◽  
M. D. Harriger ◽  
...  

1993 ◽  
Vol 105 (4) ◽  
pp. 1079-1084 ◽  
Author(s):  
M. De Luca ◽  
W. Siegrist ◽  
S. Bondanza ◽  
M. Mathor ◽  
R. Cancedda ◽  
...  

The combined action of cholera toxin (CT)-dependent activation of the adenylate cyclase signaling pathway, stimulation of protein kinase C, and activation of the tyrosine kinase activity of cell surface receptors and proto-oncogene products, have been shown to stimulate melanocyte proliferation. However, natural factors responsible for the optimal stimulation of normal human melanocyte growth, either isolated or co-cultured with keratinocytes, remain largely unknown. alpha MSH (alpha melanocyte stimulating hormone) has previously been shown to bind to murine and human melanoma cells and to stimulate their adenylate cyclase and tyrosinase activity. In contrast, very little is known about the presence and function of alpha MSH receptors in normal human melanocytes. We now report that alpha MSH: (i) binds to normal human melanocytes through a single class of high-affinity receptors; (ii) does not induce per se melanocytes to enter the S-phase of the cell cycle; (iii) does indeed stimulate melanocyte proliferation in a dose-dependent fashion; but its stimulatory effect requires bFGF and/or the activation of protein kinase C.


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