摘要:

Guanosine is shown to dramatically alter the pigment phenotype of axolotls by suppressing melanization and enhancing the biosynthesis and deposition of purine‐derived pigments. Phenotypic changes caused by guanosine are manifested by altered chromatophore differentiation patterns such that few black pigment cells (melanophores) differentiate (and those that do are punctate and necrotic in appearance), whereas the development of yellow (xanthophore) and reflecting (iridophore) pigment cells is enhanced. Mechanisms for changes in chromatophore differentiation, and thus pattern formation, are discussed, including the possibility that pigment cells may undergo transdifferentiation in viv

ISSN:0893-5785    

DOI:10.1111/j.1600-0749.1987.tb00532.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

Using a sensitive and selective culture system for human epidermal melanocytes, we have demonstrated that the morphologic changes induced by addition of phorbol 12‐tetradecanoate 13‐acetate (TPA) to proliferating newborn melanocytes are associated with induction of nerve growth factor (NGF) receptors, as measured by messenger RNA (mRNA) levels and protein accumulation and by cell surface immunofluorescent staining. Growth factor deprivation or addition of NGF similarly results in NGF receptor induction. NGF is believed to function in vivo and in vitro as a survival factor for many neural crest‐derived cells and has been demonstrated to promote specific neural cell functions ranging from neurite outgrowth to enzyme induction, but to date no role for NGF has been identified with regard to normal human melanocytes. Our data demonstrate that, given appropriate stimulation, cultured human melanocytes may express the NGF receptor gene and therefore suggest that NGF may modulate human melanocyte behavior in vivo. This first demonstration of a growth factor receptor on human melanocytes provides an important opportunity to explore signal transduction relevant to their growth, differentiation, and malignant transform

ISSN:0893-5785    

DOI:10.1111/j.1600-0749.1988.tb00793.x

出版商:Blackwell Publishing Ltd    

年代:1988

数据来源: WILEY

摘要:

Mouse melanoma cells, B16‐C2M in monolayer culture were treated with either lysosomotropic agent, 10 mM NH4Cl, or 20 μM chloroquine, an ionophore, or 10 μm monensin for 3 h at 37°C, and examined with regard to the site of melanin deposition and numbers of melanized (type 1) and unmelanized (type 2) melanosomes under a transmission electron microscope. The numbers of these two types of melanosomes were counted on electron micrographs of thin sections of 20 to 40 cells for each experimental group and expressed in terms of number per unit area of sectioned cytoplasm. Although most melanosomes were largely swollen in monensin‐treated cells, melanin deposition was apparently confined in melanosomes in all experimental groups. The compound melanosomes were scarcely found. The mean population density (number per unit cytoplasmic area) of type 1 melanosomes was highest in the NH4Cl‐treated cell group followed by monensin‐treated, chloroquine‐treated, and control cell groups. When the relative abundance of type 1 melanosomes was expressed as a fraction of total number of type 1 and 2 melanosomes (melanosomal maturation index, MMI), the differences were much more evident. Type 1 melanosomes were found in every cell (MMI ≠ 0) of the groups treated with NH4Cl and chloroquine only, which suggested the existence of a subpopulation of cells responsive to lysosomotropic agents but not to monensin in regard to melanosome maturation. All these findings indicate that the stimulation of melanogenesis proceeds mainly through maturation of preexisting melanosomes under th

ISSN:0893-5785    

DOI:10.1111/j.1600-0749.1987.tb00533.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

Since the discovery in 1967 of the phaeomelanin pathway the regulatory role of sulfhydryl compounds in epidermal melanin pigmentation has been a major focus in pigment cell research. The current state of knowledge in the field is briefly discussed, with special reference to some recent studies extending the possible targets of sulfhydryl compounds to pigment intermediates beyond the dopaquinone stage.

ISSN:0893-5785    

DOI:10.1111/j.1600-0749.1988.tb00794.x

出版商:Blackwell Publishing Ltd    

年代:1988

数据来源: WILEY

摘要:

The neuropeptides methionine enkephalin and FMRFamide, when injected into intact fiddler crabs,Uca pugilator, produce dark adaptation of the distal retinal pigment. Furthermore, both neuropeptides stimulate release of distal retinal pigment dark‐adapting hormone activity from the isolated eyestalk neuroendocrine complex. It is hypothesized that both neuropeptides, when injected into intact fiddler crabs, act only indirectly on the distal retinal pigment, by stimulating release of this dark‐adapting horm

ISSN:0893-5785    

DOI:10.1111/j.1600-0749.1987.tb00534.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

Melanocytes contain several substances formed by the nucleophilic addition of cysteine to dopaquinone. 5‐S‐Cysteinyldopa is the quantitatively dominant catecholic amino acid belonging to this group of compounds. Glutathione is the thiol most abundantly present in all cells studied, and the reactivity of the SH‐group of this tripeptide with dopaquinone is about one‐third that of cysteine. However, the amount of glutathionyldopa is at least two orders of magnitude less than that of cysteinyldopa in the melanocyte. A rapid metabolism of glutathionyldopa has therefore been suggested as an explanation for the above‐mentioned findings. The enzyme responsible for hydrolysis of the γ‐glutamyl bond of glutathione, γ‐glutamyltranspeptidase, is present in the melanocyte, but in small quantities. Furthermore, S‐cysteinylglycinyldopa, which is the product of hydrolysis by γ‐glutamyltranspeptidase, is found in only very small amounts. These facts taken together contradict the hypothesis that S‐cysteinyldopas in the melanocyte are formed from S‐glutathionyldopas. The present investigation on IGR1 melanoma cells was performed by in situ derivatization of thiols with monobromobimane. Quantitation of the stable bimane adducts of cysteine and glutathione was achieved by reverse‐phase high‐performance liquid chromatography with fluorimetric detection. The concentration of reduced cysteine in the melanocytes was found to be a few percent of that of reduced glutathione. The quantities of 5‐S‐cysteinyldopa, 5‐S‐glutathionyldopa, cysteine, and glutathione observed in the cultured melanoma cells could best be explained by a pronounced compartmentalization of cysteine within the melanocyte, with a high cysteine concentration at t

ISSN:0893-5785    

DOI:10.1111/j.1600-0749.1988.tb00795.x

出版商:Blackwell Publishing Ltd    

年代:1988

数据来源: WILEY

摘要:

The calcium ionophore, A231187, induces a Ca2+‐dependent movement (dispersion) of melanosomes within skin melanophores of the lizard,Anolis carolinensis, in vitro. The effects of A23187 are irreversible, since after repeated rinsing of the skins in the absence of the ionophore they will always darken in Ringer containing Ca2+but will immediately lighten when transferred to Ca2+‐free Ringer. These results suggest that the ionophore is irreversibly localized to the melanophore membrane and that its melano‐some‐dispersing effect is continuously dependent upon extracellular

ISSN:0893-5785    

DOI:10.1111/j.1600-0749.1987.tb00535.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

Further advances leading to more sophisticated and effective suppression of melanogenesis and melanoma growth based on clarification and utilization of common vital factors involved in both processes are reviewed. Induction of depigmentation has been achieved by both glycosylation and its processing inhibitors, which have been found to be critical for the maturation and transport of tyrosinase from ribosomes through GERL‐coated vesicles into premelanosomes. Kojic acid, a copper chelating melanogenic inhibitor, can induce inhibition of isolated tyrosinase activity as well as melanization in living pigment cells in in vitro and in vivo systems. This depigmenting effect was found to be due to a concurrent decrease in both eu‐ and pheomelanin formation. Malignant melanoma principally has accentuated melanosome genesis, which has been utilized to accumulate selectively10B into melanoma cells using10B‐dopa analogue. Subsequent thermal neutron irradiation induces10B(n, α)7Li reaction which releases high LET particles within a range of 10–14 μm thus erradicating selectively melanoma at the cellular level. This new therapy has been applied to a human melanoma lesion for the first time, and a successful therapeutic effect on melanoma has been

ISSN:0893-5785    

DOI:10.1111/j.1600-0749.1988.tb00796.x

出版商:Blackwell Publishing Ltd    

年代:1988

数据来源: WILEY

ISSN:0893-5785    

DOI:10.1111/j.1600-0749.1987.tb00536.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

Alpha‐melanotropin (alpha‐melanocyte stimulating hormone, alpha‐MSH) is a hormone produced by the pituitary gland of most vertebrate animals. This melanotropic peptide, Ac‐Ser‐Tyr‐Ser‐Met‐Glu‐His‐Phe‐Arg‐Trp‐Gly‐Lys‐Pro‐Val‐NH2, regulates melanin pigmentation of the skin of some mammals. Although MSH may be absent from the human pituitary gland, this peptide can stimulate pigment formation in human skin. We have synthesized several analogues of alpha‐MSH, which are superpotent, prolonged‐acting, and resistant to inactivation by serum enzymes. One such analogue, [NLe4,D‐Phe7]alpha‐MSH, has proven particularly useful in a number of physiological studies. In addition, some [Nle4,D‐Phe7]‐substituted fragment analogues of MSH are even more active than the native hormone, alpha‐MSH. For example, these analogues are 100–1,000 times more active than alpha‐MSH in stimulating S‐91 mouse melanoma tyrosinase activity in vitro. We have successfully labeled one such peptide to high specific activity; this melanotropin, [3H]‐Ac‐[Nle4,D‐Phe7]alpha‐MSH4–11NH2, has been shown by others to bind to B16 melanoma cells. We have also conjugated several ligands (fluorescein and biotin) to [Nle4,D‐Phe7]alpha‐MSH. These melanotropin conjugates might prove useful for melanotropin receptor studies and for the clinical localization of metastatic melanoma. We have demonstrated that [Nle4,D‐Phe4]alpha‐MSH can be topically applied and transdermally delivered across the skin of mice and humans in vitro, as determined by bioassay and RIA. Initial toxicologic studies indicate that the analogue is nontoxic to mice and is not mutagenic. Studies are underway to determine whether this analogue may prove useful as a “tanning hormone” for increasing the pigmentation of light‐skinned individua

ISSN:0893-5785    

DOI:10.1111/j.1600-0749.1988.tb00797.x

出版商:Blackwell Publishing Ltd    

年代:1988

数据来源: WILEY