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)

Proopiomelanocortin (POMC) is the precursor for adrenocorticotropic hormone, melanocyte-stimulating hormones, beta-lipotropic hormone (beta LPH), and beta endorphin. These peptides can function as neurotransmitters, modulate immune responses, and affect melanogenesis. We investigated POMC expression and protein processing in normal human keratinocytes. On Northern blot analysis, the baseline expression of the 1.2-kb POMC transcript was upregulated by ultraviolet radiation (UVR) or by stimulation with interleukin-1 alpha (IL-1 alpha) or phorbol 12-tetradecanoate 13-acetate (TPA). On Western blot analysis, POMC, beta LPH, and beta-endorphin were detected in cell extracts under baseline conditions. beta LPH level increased substantially after UVR, IL-1 alpha, or TPA. Within 36 h after TPA stimulation, beta-endorphin became undetectable in cell extracts, coinciding with an increase of beta-endorphin-immunoreactive protein in the culture medium. Our data establish that keratinocytes synthesize POMC protein as well as its derivatives beta LPH and beta-endorphin, and that this process is modulated by TPA, IL-1A, and UVR. beta LPH and beta-endorphin of keratinocyte origin may thus be involved in melanogenesis and/or immunomodulation in the skin after sun exposure, and their release into the circulation may also have systemic effects.
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PMID:Proopiomelanocortin gene product regulation in keratinocytes. 861 3

PO-B was originally characterized as a transcriptional regulatory factor of the pro-opiomelanocortin (POMC) gene; however, it has become increasingly clear that this protein may be active in tissues outside the pituitary, since it is present in diverse cell types, including differentiated HL-60 promyelocytic leukemia cells. We previously showed that PO-B DNA-binding is progressively induced during differentiation of promyelomonocytic leukemic HL-60 cells to the macrophage-like lineage (with phorbol esters). We now report that PO-B DNA-binding in HL-60 cells is similarly induced during differentiation to the granulocytic lineage (with either retinoic acid or dimethylsulfoxide). Either a genetic or pharmacologic blockade of HL-60 differentiation prohibited these inductive effects. These studies have prompted our interest in the dynamics of other transcription factor changes during HL-60 differentiation. Of these, we observed that another transcription factor (AP-1) is also robustly induced at the DNA-binding level during macrophage-like HL-60 differentiation, but not during granulocytic differentiation. Conversely, the DNA-binding of the transcription factor AP-2 was slightly reduced by TPA-induced HL-60 differentiation but unchanged during granulocyte differentiation. From these data, we conclude that the induction of PO-B DNA binding is a general marker of HL-60 myelomonocytic differentiation, but that qualitative aspects of the induction of additional distinct transcription factors, such as AP-1, may contribute to lineage-specific determinants of cell fate.
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PMID:Effects of TPA, bryostatin 1, and retinoic acid on PO-B, AP-1, and AP-2 DNA binding during HL-60 differentiation. 913 88

Skins of Potamotrygon reticulatus are light in color in vitro, exhibiting punctate melanophores. Alpha-Melanocyte stimulating hormone (EC(50) = 4.58 x 10(-9) M) and prolactin (EC(50) = 1.44 x 10(-9) M) darken the skins in a dose-dependent manner. The endothelins ET-1, ET-2 and ET-3, and the purines, ATP, and uracil triphosphate (UTP) were not able to induce either skin lightening or darkening. Forskolin and the calcium ionophore A23187 promoted a dose-dependent darkening response, whereas N(2), 2'-O-dibutyryl guanosine 3'-5'-cyclic monophosphate (db cyclic GMP), phorbol-12-myristate-13-acetate (TPA), and 1-oleoyl-2-acetyl-sn-glycerol (OAG) were ineffective. The maximal response obtained with the calcium ionophore A23187 was only 76% of maximal darkening. These results indicate that the cyclic adenosine 3'-5'-monophosphate (cAMP) pathway is probably involved in the pigment dispersion of P. reticulatus melanophores. Other experiments should be done to further investigate how cytosolic calcium may be physiologically increased, and the existence of a putative cross-talk between calcium and cAMP signals. In conclusion, the only hormones effective on P. reticulatus melanophores were prolactin and alpha-MSH. No aggregating agent has been shown to antagonize these actions. Prolactin effect on elasmobranch melanophores adds a novel physiological role to this ancient hormone. J. Exp. Zool. 284:485-491, 1999.
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PMID:Elasmobranch color change: A short review and novel data on hormone regulation. 1046 85

Proopiomelanocortin (POMC) is a protein that is posttranslationally processed to yield POMC peptides. The main site of POMC expression is the anterior pituitary lobe but many other sources have been identified. There is evidence that the skin produces POMC peptides, although their roles have not yet been defined. In the skin, regulation of POMC gene expression is known to be hair-cycle dependent, and it is localized to the sebaceous gland. In particular, beta-endorphin, a POMC peptide, has been shown to be modulated by TPA, IL-1 alpha, and ultraviolet radiation in keratinocytes. These results were obtained by examination of POMC mRNA levels using the Northern blot method; beta-endorphin protein production by the Western blot method on cultured cells; and immunocytochemistry for tissue preparations. This report represents an approach to use immunocytochemistry to quantify beta-endorphin production in cultured human keratinocytes. Additionally, we examined whether exposure to 20 mJ ultraviolet B radiation (UVB) and/or UVA could influence beta-endorphin production in these cells. Keratinocytes were grown in monolayers, in serum-free medium, fixed, and incubated with antiserum to whole synthetic beta-endorphin. Fluorescence microscopy was performed with a confocal laser scanning microscope. The integrated level of fluorescence was evaluated in n = 18 +/- 8 individual cells, and this was assumed to be proportional to beta-endorphin content. High variability was observed in the fluorescence intensity among cells. No significant differences between control and UVB- or UVA + UVB-treated cells was found. Similar results were produced by using brefeldin A, a compound that disrupts the secretory pathway, eliminating the possibility that the absence of a difference between beta-endorphin content in the treated and control cells was due to secretion of the peptide into the medium. We conclude that: (1) beta-endorphin or beta-endorphin-like peptides are produced in human keratinocytes and are readily detected by immunocytochemistry; (2) under the conditions tested, UVA and/or UVB did not increase beta-endorphin-like immunoreactivity in these cells.
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PMID:An immunocytochemical approach to the study of beta-endorphin production in human keratinocytes using confocal microscopy. 1081 43

Antipsychotic drugs can regulate transcription of some genes, including those involved in regulation of hypothalamic-pituitary-adrenal (HPA) axis, whose activity is frequently disturbed in schizophrenic patients. However, molecular mechanism of antipsychotic drug action on the corticotropin-releasing hormone (CRH) gene activity has not been investigated so far. This study was undertaken to examine the influence of conventional and atypical antipsychotic drugs on the CRH gene promoter activity in differentiated Neuro-2A cell cultures stably transfected with a human CRH promoter fragment linked to the chloramphenicol acetyltransferase (CAT) reporter gene. It has been found that chlorpromazine (0.1-5.0 microM), haloperidol (0.5-5.0 microM), clozapine (1.0-5.0 microM), thioridazine (1.0-5.0 microM), promazine (5.0 and 10 microM), risperidone (5.0 and 10.0 microM), and raclopride (only at the highest used concentrations, ie 30 and 100 microM) present in culture medium for 5 days inhibited the CRH-CAT activity. Sulpiride and remoxipride had no effect. Since CRH gene activity is most potently enhanced by cAMP/protein kinase A pathway, the effect of antipsychotics on the forskolin-induced CRH-CAT activity was determined. Chlorpromazine (1.0-5.0 microM), haloperidol (1.0-5.0 microM), clozapine (1.0-5.0 microM), thioridazine (3.0 and 5.0 microM), and raclopride (30 and 100 microM), but not promazine, sulpiride, risperidone, and remoxipride, inhibited the forskolin-stimulated CRH gene promoter activity. A possible involvement of protein kinases in chlorpromazine and clozapine inhibitory action on CRH activity was also investigated. It was found that wortmannin (0.01 and 0.02 microM), an inhibitor of phosphatidylinositol 3-kinase (PI3-K), significantly attenuated the inhibitory effect of chlorpromazine and clozapine on CRH gene promoter activity. In line with these results, a Western blot study showed that these drugs increased phospho-Ser-473 Akt level, had no effect on total Akt, and decreased glycogen synthase kinase-3beta level. Additionally, we found that clozapine decreased protein kinase C (PKC) level and that its action on CRH activity was attenuated by PKC activator (TPA, 0.1 microM). The obtained results indicate that inhibition of CRH gene promoter activity by some antipsychotic drugs may be a molecular mechanism responsible for their inhibitory action on HPA axis activity. Clozapine and chlorpromazine action on CRH activity operates mainly through activation of the PI3-K/Akt pathway. Moreover, PKC-mediated pathway seems to be involved in clozapine action on CRH gene activity.
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PMID:Antipsychotic drugs inhibit the human corticotropin-releasing-hormone gene promoter activity in neuro-2A cells-an involvement of protein kinases. 1620 82


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