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)

Melanocyte stimulating hormone (alpha-MSH, alpha-melanotropin),Ac-Ser-Tyr-Ser-Met-Glu-His-Phe-Arg-Trp-Gly-Ly-Pro-Va l-NH2, regulates melanogenesis within epidermal melanocytes of many animals. An MSH analogue ([Nle4,D-Phe7]alpha-MSH) that exhibits superpotency and prolonged biological activity has been synthesized, biologically characterized, and is presently in clinical trials to determine its possible clinical use in tanning of the skin. It also has potential for the diagnosis, localization, and chemotherapy of melanoma. The effects of this analogue on the growth, metastatic behavior, and invasive potential of a melanotic variant of Cloudman S-91 murine melanoma are reported here. In an intracutaneous murine model of melanoma cell tumor growth, the analogue did not increase primary tumor growth (size) after the period of administration of the peptide hormone analogue and did not affect spontaneous lung metastases. Survival times for the control and melanotropin-treated groups were similar, suggesting that overall tumor burden was not affected by treatment with the hormone analogue. Last, melanoma cell invasion through a human amniotic basement membrane in vitro was not enhanced compared to untreated cells.
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PMID:Effects of a melanotropic peptide on melanoma cell growth, metastasis, and invasion. 133 2

Melanocytes and melanoma cells are known to possess receptors for melanocyte stimulating hormone (MSH). A cDNA clone, designated 11D, has been isolated from human melanoma cells and encodes a MSH receptor. The cloned cDNA encodes a 317 amino acid protein with transmembrane topography characteristics of a G-protein-coupled receptor, but it does not show striking similarity to already published sequences of other G-protein-coupled receptors. When 11D cDNA is expressed in COS-7 cells, it binds an 125I-labelled MSH analogue (NDP-MSH) in a specific manner. The bound ligand could be displaced by melanotropic peptides, alpha-MSH, beta-MSH, gamma-MSH and ACTH (adrenocorticotropic hormone), but not by the non-melanotropic peptide, beta-endorphin. This is the first report of the cloning of the receptor gene of the melanotropin receptor family.
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PMID:Molecular cloning and expression of the human melanocyte stimulating hormone receptor cDNA. 870 68

We studied the pigmentary activity of the peptides gamma 1, gamma 2 and gamma 3 melanocyte stimulating hormone (MSH), which differ in the structure of their C-termini, using hamster and mouse melanoma cell lines responsive to beta-MSH by increasing tyrosinase activity. Gamma 1-MSH alone or in combination with beta-MSH had no effect on either cell line. Gamma 2-MSH alone was biologically inactive but potentiated beta-MSH stimulation of tyrosinase activity. Gamma 3-MSH at high concentration (10 microM) induced tyrosinase activity and dendrite formation in the hamster melanoma line. When added together with beta-MSH, gamma 3-MSH partially inhibited the tyrosinase activity response to beta-MSH. Thus, gamma-MSH peptides have low intrinsic melanotropic activity in mammalian melanoma cells; the specific pigmentary responses appear to be affected by the structure of the C-terminal portion.
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PMID:Melanotropic activity of gamma MSH peptides in melanoma cells. 155 5

The expression of alpha melanocyte stimulating hormone (MSH) has been investigated in two variants of the B16 murine melanoma. The presence of MSH was demonstrated by immunohistochemical methods using anti-MSH antibodies. The low metastasis variant B16-F1, which grows as an encapsulated non-invasive tumour, showed no alpha-MSH immunoreactivity. In contrast, the high metastasis variant BL6 was found to be alpha-MSH positive and the immunoreactivity was found predominantly in the peripheral invading zones of the tumour.
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PMID:Expression of alpha-melanocyte stimulating hormone and the invasive ability of the B16 murine melanoma. 158 May 57

We have previously reported the genetic construction and properties of a fusion protein which was composed of the enzymatically active and membrane translocation domains of the diphtheria toxin and the receptor-specific ligand alpha-melanocyte-stimulating hormone (alpha-MSH) (Murphy, J.R., Bishai, W., Borowski, M., Miyanohara, A., Boyd, J., and Nagle, S. (1986) Proc. Natl. Acad. Sci. U.S.A. 83, 8258-8262). While this fusion toxin was found to be selectively toxic for MSH receptor-bearing cells in vitro, it was subject to profound proteolytic degradation in recombinant Escherichia coli making purification difficult. We now report that the deletion of diphtheria toxin fragment B sequences between Thr387 and His485 results in a protease-resistant form of the fusion toxin, DAB389-alpha-MSH. We show that DAB389-alpha-MSH is expressed in high yield in recombinant Escherichia coli, that it is readily purified from crude bacterial lysates by immunoaffinity and high performance liquid chromatography, and its cytotoxic activity toward both human and murine malignant melanoma cell lines is mediated through the MSH receptor.
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PMID:Diphtheria toxin-related alpha-melanocyte-stimulating hormone fusion toxin. Internal in-frame deletion from Thr387 to His485 results in the formation of a highly potent fusion toxin which is resistant to proteolytic degradation. 164 90

Three different monoiodinated radioligands of alpha-MSH (alpha-melanocyte-stimulating hormone) were compared in a binding assay with human D10 melanoma cells: [Tyr(125I)2]-alpha-MSH, [Tyr(125I)2,NIe4]-alpha-MSH, and [Tyr(125I)2,NIe4,D-Phe7]-alpha-MSH. They were prepared either by the classical chloramine T method or by the Enzymobead method. A simple and rapid purification scheme was developed consisting of a primary separation on reversed-phase C18 silica cartridges immediately after the iodination, followed by HPLC purification before each binding experiment. Biological testing of the three radioligands showed that they all retained high melanotropic activity in the B16 melanin assay and the Anolis melanophore assay. However, in human D10 melanoma cells, [Tyr(125I)2,NIe4]-alpha-MSH led to a high degree of non-specific binding to the cells which could not be displaced by excess alpha-MSH and only partially by [NIe4]-alpha-MSH. The [Tyr(125I)2,NIe4,D-Phe7]-alpha-MSH tracer gave similar results but with a much lower proportion of non-specific binding. On the other hand, [Tyr(125I)2]-alpha-MSH proved to be an excellent radioligand whose non-specific binding to the D10 cells was not higher than 20% of the total binding.
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PMID:Biologically active monoiodinated alpha-MSH derivatives for receptor binding studies using human melanoma cells. 165 37

It has been shown that alpha-MSH inhibits the growth of amelanotic cells of human malignant melanoma (BRO) without their melanization or the expression of tyrosinase activity. alpha-MSH changed the activity of cytosol and microsomal forms of phosphatidyl inositol kinase and phosphatidyl inositol-4-phosphate kinase determining the concentration of phosphatidyl inositol-4-phosphate and phosphatidyl inositol-4,5-bisphosphate. It also induced an "outburst" in the levels of myo-inositol phosphates (mono-, bis- and 1,4,5-trisphosphates). Changes in the levels of myo-inositol phosphates occurred within seconds, and are suggested to play a certain part in the hormonal regulation of melanoma cell growth.
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PMID:Melanocyte-stimulating hormone (alpha-MSH) inhibits the growth of human malignant melanoma cells with the induction of phosphatidyl inositol and myo-inositol phosphate levels. 166 68

Previous work from our laboratory has shown that both cyclic AMP and calcium/calmodulin appear to be involved in the regulation of melanogenesis in murine B16 melanoma cells. In these cells as in murine Cloudman S91 cells, melanogenic responsiveness to melanocyte-stimulating hormone (MSH) varies with cell density in culture. Our objective in this study was to learn more about the intracellular systems involved in the control of melanogenesis, particularly the role played by calcium. The melanogenic response to alpha MSH was compared to the response to drugs affecting intracellular free calcium and calmodulin over a range of cell densities in B16F1 cells. alpha MSH-stimulated melanin production was extremely density-dependent but alpha MSH-stimulated cyclic AMP production was independent of cell density. The melanogenic response to agents that increased intracellular calcium (A23187) or inhibited intracellular calmodulin varied with cell density. A drug (TMB8) that lowered intracellular free calcium, however, increased melanogenesis independently of cell density. At high cell density it was found that an elevation in calcium decreased melanogenesis, whereas agents that reduced calcium or inhibited calmodulin activity increased melanogenesis. At low cell density, however, the inhibitory response to A23187 was lost and in some experiments even stimulated melanogenesis. These data suggest that the calcium/calmodulin signalling system has an inhibitory influence on melanogenesis, and its expression, which depends upon cell density, may also modulate the response to stimulatory agents such as alpha MSH.
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PMID:Evidence for a calcium/calmodulin involvement in density-dependent melanogenesis in murine B16 melanoma cells. 166 9

Four fatty acids (FA, palmitic, myristic, decanoic, hexanoic) were individually conjugated to the N-terminus of the alpha-MSH fragment analog, H-Asp5-His6-D-Phe7-Arg8-Trp9-Lys10-NH2. This resulted in enhanced potency of the conjugates (compared to the unconjugated melanotropin analog) as determined in the lizard skin bioassay and in the mouse melanoma cell tyrosinase bioassay. The shorter conjugates of hexanoic and decanoic acid were at least equipotent to alpha-MSH in the lizard skin bioassay, whereas the longer myristoyl and palmitoyl analogs were 100 times less active. The myristoyl and palmitoyl conjugates exhibited a "creeping" potency in the lizard skin bioassay-that is, potency of the peptides increased with time in contact with the skins. These observations may be related to the more lipid nature of these FA-conjugates. In the tyrosinase assay, the conjugates were 10-100 times more active than alpha-MSH or the unconjugated analog. Each of the FA-melanotropic peptide conjugates exhibited prolonged (residual) melanotropic activity in both the lizard skin and melanoma cell bioassays. In other words, after removal of the melanotropin conjugates from contact with the skins or cells, responses were still manifested for hours or days thereafter. As little as 1 hr of contact with melanoma cells resulted in enhanced enzyme activity as measured 48 hr later. Since the conjugates, but not H-[Asp5, D-Phe7, Lys10]alpha-MSH5-10-NH2, exhibited prolonged activity, the conversion of reversible agonists to irreversible agonists was demonstrated.
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PMID:Biological activities of melanotropic peptide fatty acid conjugates. 166 21

A conjugate made of alpha-MSH as a drug carrier and melphalan has been designed in order to target human melanoma cells. Iodination of the alpha-MSH moiety led to a relatively stable tracer which could be easily separated and analysed by reverse phase high pressure liquid chromatography. The conjugate was found to be unstable at neutral pH and a serious denaturation can take place at concentrations exceeding 100 micrograms/ml, especially in plasma. Receptor-mediated cytotoxicity has been shown by the use of cultured alpha-MSH receptor positive/negative cells as well as in vivo B16 murine melanoma model. Body distribution and uptake of the labelled compound were unaltered as compared to those of labelled free hormone. alpha-MSH receptor recognition properties also remained unchanged with a better apparent affinity of the conjugate probably due to the alkylating activity of melphalan itself. Using human melanoma dendritic cells expressing more than 10,000 alpha-MSH binding sites per cell as an in vitro model, we were able to demonstrate higher cytotoxicities as compared to melphalan-treated cells. In contrast, melanoma cells with low receptivity did not show higher cytotoxicity. P388D1 mouse plasmocytoma cells lacking receptors were much more sensitive to melphalan than the conjugate. This phenomenon appeared to be related with the number of binding sites expressed at the time of the experiment as well as cell differentiation and the doubling time. Our findings strongly support the concept of a receptor-mediated cytotoxicity and may enable the in vivo melphalan delivery to target tissues to be increased, achieving an improvement of drug penetration inside melanoma cells.
Melanoma Res
PMID:Human melanoma targeting with alpha-MSH-melphalan conjugate. 166 32


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