摘要:

Dopachrome, an intermediate in melanin biosynthesis, exhibits some unusual properties. At physiologic pH (e.g., pH 6‐8) it is unstable and spontaneously loses its carboxyl group to form 5,6‐dihydroxyindole (DHI(and CO2. However, over this same pH range, if various metals or a melanocyte‐specific enzyme are present, it rapidly rearranges to its isomer form—5,6‐dihydroxyindole‐2‐carboxylic acid (DHICA)—which is far more stable than dopachrome in its ability to retain the carboxyl group. Whether or not the carboxyl group is retained could have important implications for the regulation of melanogenesis, since in the presence of oxygen DHI spontaneously forms a black precipitate, whereas DHICA forms a golden‐brown solution. The solubility of “DHICA‐melanin” is due to the presence of carboxyl groups, which provide negative charges and hydrophilicity. Thus, in vivo, the extent to which dopachrome is converted to DHI or DHICA may well influence the solubility and color of the melanin formed. The purpose of this article is to review recent findings in these areas and to discuss the possible significance of dopachrome conversion in the regulation of melanogenesis and color formation.SUMMARYThis review has explored events in the melanogenic pathway that are under regulatory control after the formation of dopachrome. No attempt was made to include the regulation of pheomelanin synthesis, although the same basic questions should exist for both pheo‐ and eumelanogenesis. It seems clear that the earlier concepts of melanogenesis, wherein tyrosinase was the only regulatory enzyme, are incorrect, at least for mammals. Elucidating the newly described pathways will take considerable research effort and ingenu

ISSN:0893-5785    

DOI:10.1111/j.1600-0749.1991.tb00315.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

ISSN:0893-5785    

DOI:10.1111/j.1600-0749.1991.tb00316.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

MCH (melanin concentrating hormone) is a heptadecapeptide, Asp‐Thr‐Met‐Arg‐Cys‐Met‐Val‐Gly‐Arg‐Val‐Tyr‐Arg‐Pro‐Cys‐Tip‐Glu‐Val, which stimulates melanosome (melanin granule) aggregation to a perinuclear position within teleost fish integumental melanocytes, resulting in lightening of the skin. The mechanisms of action of MCH are unknown.Drugs that affect the diacylglycerol/inositol triphosphate pathway were used to investigate the possible roles of this pathway in the mechanisms of action of MCH onSynbranchus marmoratus(teleost) melanocytes. The shift of the dose‐response curve to MCH in the presence of various concentrations of 4‐bromophenacyl bromide and neomycin sulphate, phospholipase C inhibitors, suggests that phospholipase C is stimulated after MCH receptor activation. Low concentrations (10−9to 10−8M) of the phorbol ester TPA exhibited MCH‐like activity, eliciting a dose‐dependent melanosome aggregation. Higher doses, however, displaced to the right the dose‐response curve to MCH, as did the protein kinase C inhibitors, dibucaine and 1‐(5‐isoquinolinylsulfonyl)‐2‐methylpiperazine (H‐7). These results support the assumption that protein kinase C mediates the pigment aggregating activity of MCH.Both MCH and norepinephrine lightening actions were abolished by beta‐glycerophosphate, a phosphatase inhibitor, suggesting that a protein dephosphorylation occurs during melanosome aggregation, and is, therefore, a common event triggered by MCH and norepinephrine, although both agonists act through separat

ISSN:0893-5785    

DOI:10.1111/j.1600-0749.1991.tb00317.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

Chronically sun‐exposed facial skin of three females aged 68, 71, and 78 years, and of a male aged 78, was examined by electron microscopy in order to study the condition of the epidermal melanocytes. Considerable heterogeneity of morphological and functional characteristics of the cells was observed. The majority of melanocytes were large, active, with occasionally tabulated or double nuclei, an appearance indicative of hyperstimulation. Some cells exhibited an appearance of having reached the end of an active life cycle and were labelled “aged.” Others, in the upper end of the outer root sheath of hair follicles and adjacent interfollicular epidermis, presented a typically inactive appearance, indistinguishable from that of fetal melanocytes, or of those in unexposed skin of younger subjects. A cell with indented nucleus, fully melanised melanosomes, and hypertrophie Golgi apparatus was sporadically seen. Minute foci of dissociation of keratocytes were present, and melanocytes included in these were frequently disrupted. Swelling of mitochondria and cytoplasmic lipid droplets occurred sporadically within all the above variants of melanocytes. It proved difficult to establish criteria of specific sun damage of melanocytes. It is suggested that either the melanocytes exhibiting stimulation or the relatively inactive ones could be the precursors of the proliferating cells of lentigo ma

ISSN:0893-5785    

DOI:10.1111/j.1600-0749.1991.tb00318.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

Melanin contains melanin‐free radicals and can both absorb and produce additional free radicals and active oxygen species on exposure to various stimuli. Yet its role in the radiation responses of malignant melanoma has been little studied. In this report, three subclones of Cloudman S91 mouse melanoma clone PC1A varying in constitutive melanin content were compared with respect to killing by gamma irradiation. Radiation responses correlated with melanin content. The least melanotic line, S91/amel, was most sensitive and the most melanotic line, S91/I3, was most resistant. Curve fitting using the linear‐quadratic model suggests that S91/amel is killed only by single event inactivations; S91/I3, only by double event inactivations; and S91/M1B, with intermediate melanin and radiation response, by both types of inactivations. Split dose experiments confirmed a lack of immediate split dose recovery in S91/amel and its existence in S91/I3. Potentially lethal damage and its repair could be demonstrated in both S91/amel and S91/I3. Double strand break (DSB) induction was evaluated as a function of gamma ray dose in DNA of S91/I3 and S91/amel, as well as in EMT6, a mouse mammary cancer line that lacks tyrosinase and melanin. The rates of induction were proportional to cellular melanization, i.e., the rate of DSB induction was greatest in S91/I3, least in EMT6. Levels of thioredoxin reductase (TR), glutathione reductase (GR), superoxide dismutase (SOD), and catalase (CAT) were determined in S91/amel and S91/I3. TR was the same in both cell lines, while the other three enzymes were 3‐ to 4‐fold lower in S91/amel. The results suggest that 1) melanin can act as a radiosensitizer of DNA damage and, 2) the presence of moderate constitutive levels of melanin in cells may effect radiation resistance by indirect means, possibly by causing cells to maintain high levels of antioxidant defenses and/or DNA repair

ISSN:0893-5785    

DOI:10.1111/j.1600-0749.1991.tb00319.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

We have distinguished two types of melanocyte within the intermediate layer of the stria vascularis in the cochlea of normally pigmented mice: light and dark intermediate cells. The light intermediate cells are present in the stria from birth and have the typical appearance of a melanocyte. They are large and dendritic with electron‐lucent cytoplasm containing numerous vesicles that show tyrosinase activity, and pigment granules in various stages of development. These granules have the ultrastructural and histochemical characteristics of premelanosomes and melanosomes. The light intermediate cells persist throughout life, but less frequently contain pigment in older animals. The dark intermediate cells, present only in adult mice, vary considerably in number and distribution between animals. Pigment granules, bound within an electron‐dense acid phosphatase‐rich matrix, form the main component of the dark intermediate cells. The intermediate cells may comprise either two distinct cell populations or different developmental stages of the same cell type; ultrastructural observations suggest the latter. In young mice, light intermediate cells contain the electron‐dense matrices, which at later stages of development are found almost exclusively in dark cells. The dark intermediate cells contain few cell organelles other than pigment granules accumulated within lysosomal bodies and they often have pyenotie nuclei. These observations suggest that the dark intermediate cells are a degenerate form of the light intermediate cells. Clusters of melanosomes also occur in the basal cells, and to a much lesser extent in the marginal cells. These cells do not stain after incubation in DOPA, suggesting that they are not capable of melanin synthesis, and therefore probably acquire melanin by donation from adjacent melanocytes. Pigment clusters are also found within the spiral ligament at all stages of deve

ISSN:0893-5785    

DOI:10.1111/j.1600-0749.1991.tb00320.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

ISSN:0893-5785    

DOI:10.1111/j.1600-0749.1991.tb00321.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY