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)

DNA sequences of vertebrate genes which code for neural or neuroendocrine peptides were analysed in terms of CpG dinucleotide distribution and G+C content. The vast majority of the genes were found to contain a region with the sequence characteristics of a CpG island surrounding the 5' end. In mammalian species, the gene which codes for the neuroendocrine polypeptide pro-opiomelanocortin (POMC) was shown to be associated with two separate CpG islands: a 5' CpG island which surrounds the POMC transcription start site and a 3' CpG island which lies approximately 5 kb downstream, encompassing the third exon of POMC. Short POMC-related transcripts, known to be transcribed in the germline, were found to initiate from a promoter within the 3' CpG island. The start sites of the short POMC-related transcripts in mouse testis were mapped to the region coding for gamma MSH in exon 3, in a similar location to transcription start sites identified in other mammalian POMC genes. Similar short POMC-related transcripts were identified in both the mouse F9 embryonal carcinoma cell line and mouse embryonic stem cells, suggesting that transcription initiating within the third exon may occur very early in development. No short transcripts were detected by Northern blot hybridization in either Xenopus laevis testis or oocyte poly(A)+ RNA extracts. The Xenopus laevis POMC genes, A and B, were associated with neither a 5' nor a 3' CpG island. Hence, the presence of a 5' CpG island is not required for production of full-length transcripts from the Xenopus laevis POMC gene, but the presence of a 3' CpG island may be required for transcription to occur from the third exon.
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PMID:Transcripts and CpG islands associated with the pro-opiomelanocortin gene and other neurally expressed genes. 791 74

A variety of proteins and peptides are produced through limited proteolysis of precursors at paired basic residues. This proteolytic bioactivation is carried out by subtilisin-like proteases, called convertases. The mRNAs of several convertases are expressed during prenatal life as well as in P19 embryonal carcinoma cells, which are a model of the totipotent cells of the embryo before and at the time of implantation. To determine whether converting activities accompany convertase mRNA expression in the early embryo, we transferred the gene of pro-opiomelanocortin (POMC) into P19 cells, by lipofection, and searched for the presence of mature peptides by high-performance liquid chromatography and radioimmunoassay techniques. In P19 cells, POMC, a precursor of several endocrine peptides, is mainly processed to beta-lipotropin rather than to beta-endorphin, both peptides having been identified by their immunoreactivity, polarity, and molecular size. These results indicate that converting capacities appear early in the embryo and that they are more similar to the activity of furin and of convertase PC1 than that of convertase PC2 in their cleavage selectivity of POMC sites. Efficiency of POMC processing can reach 50%, suggesting that convertases, with other proteases, can have an important role in ontogenesis. As for other peptide precursors in endocrine cells, the conversion of POMC in P19 cells was inhibited by the biosynthetic replacement of its arginine residues by the analog canavanine. However, the incorporation of canavanine into P19 cells also inhibited peptide secretion, suggesting that inhibition of conversion in these cells as well as in endocrine cells could indirectly result from the impairment of intracellular traffic and not only from a direct inhibition of the converting activity.
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PMID:Proteolytic profile of recombinant pro-opiomelanocortin in embryonal carcinoma P19 cells: conversion to beta-lipotropin and secretion are inhibited following incubation with canavanine. 940 43

For optimal neural transplantation using gene engineering, it might be important to control the expression of the transfected gene extrinsically as required. This strategy could be very useful for the treatment of intractable pain that responds to opioids. For this purpose, we established a genetically modified embryonal carcinoma cell line (P19) in which the expression of beta-endorphin (beta-EP) could be controlled by the addition of dexamethasone. To obtain extrinsic control, we transfected the cells with pMAMneo containing mouse MMTV-LTR as a promoter and cDNA of the artificial beta-EP. The upregulation of beta-EP, through the activation of MMTV by the administration of dexamethasone, was confirmed in vitro. Then we transplanted these cells into the subarachonoid space in rats and evaluated the analgesic potential of these cells in vivo by hot plate test and formalin test. In the rats that received beta-EP-producing cells, we observed prominent analgesic effects after the transplantation for a month. The administration of naloxone blocked these effects. Intraperitoneal injection of 100 mg/kg dexamethasone further enhanced these effects by up to two times. These data indicate obvious analgesic effects of the cells after the transplantation and the possible exogenous upregulation of transfected beta-EP gene expression in vivo. The application of this technique might provide a new therapeutic approach to various neurological diseases.
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PMID:Attempted gene therapy for intractable pain: dexamethasone-mediated exogenous control of beta-endorphin secretion in genetically modified cells and intrathecal transplantation. 1103 Oct 86