Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P01189 (beta-endorphin)
 21,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Endocrine, exocrine, and neuronal cells package only a subset of their secretory products into the electron-dense secretory granules. To investigate the factors controlling selective packaging of proteins into these granules, we utilized the mouse pituitary tumor cell line, AtT-20, which retained the capability to sort adrenocorticotropic hormone (ACTH) into secretory granules in vitro. Packaging of ACTH was blocked by treatment with weak bases, but was unaffected when N-linked glycosylation or sulfation was inhibited. To test whether the targeting information is specified by sorting domains present on peptide hormone sequences, we determined if a protein could be diverted to the dense secretory granules by attachment to a peptide hormone sequence. A plasmid DNA was constructed that encoded a hybrid protein in which a fragment of a viral membrane protein was fused to the carboxy terminus of human growth hormone. AtT-20 cells transfected with the hybrid were found to target it to dense secretory vesicles efficiently. These results support the hypothesis that sorting domains on peptide hormones direct their packaging into dense secretory vesicles.
 ...
PMID:Factors controlling packaging of peptide hormones into secretory granules. 303 86

An observation from high-pressure liquid chromatography (HPLC) suggesting that monkey beta-endorphin (BE) was chemically different from human or rat BE was investigated by determining the cDNA sequence for the monkey pro-opiomelanocortin (POMC) precursor. A full-length cDNA for POMC was isolated from a Macaca nemestrina whole pituitary cDNA library. The longest open reading frame predicts a 264-residue polypeptide exhibiting the basic structure of POMC that is closely homologous to the human counterpart. The monkey BE sequence apparently diverged from the human sequence after the latter had made the His-27 to Tyr-27 change but prior to the Gln-31 to Glu-31 transition, leaving it more hydrophobic than rat or human BE, consistent with its chromatography on reverse-phase HPLC. Comparison of the monkey POMC precursor with those of other species highlights conserved domains, presumably reflecting regions of physiological activity that await elucidation.
DNA 1988 Nov
PMID:Characterization of pro-opiomelanocortin cDNA from the Old World monkey, Macaca nemestrina. 322 86

The gene encoding pro-opiomelanocortin (POMC) offers an interesting model system to study negative control of transcription in eucaryotes. Indeed, glucocorticoid hormones specifically inhibit transcription of the POMC gene in the anterior pituitary. The POMC gene is predominantly expressed in the anterior and intermediate lobes of the pituitary. However, only anterior pituitary POMC transcription is inhibited by glucocorticoids and stimulated by corticotropin-releasing hormone (CRH). Rat POMC promoter sequences required for anterior pituitary-specific expression were localized between positions -480 and -34 base pairs (bp) by DNA-mediated gene transfer into the POMC-expressing tumor cells. AtT-20. These POMC promoter sequences also confer glucocorticoid inhibition of transcription. While two of the six in vitro binding sites for purified glucocorticoid receptor identified in the rat POMC gene are within these sequences, only one is required for glucocorticoid inhibition; this binding site is located at position -63 bp in the promoter and overlaps a putative CCAAT box sequence. The DNA sequence of the POMC -63 bp receptor binding site is homologous to receptor binding sites identified in the glucocorticoid responsive element (GRE) of glucocorticoid-inducible genes. However, DNA sequence divergencies between these sites, in particular within the conserved hexanucleotide sequence 5'-TGTYCT-3', may be involved in their opposite transcriptional activity. Alternatively, binding of the receptor in the promoter proximal region of the POMC gene may inhibit transcription by a hormone-dependent repressor mechanism.
 ...
PMID:Pro-opiomelanocortin gene: a model for negative regulation of transcription by glucocorticoids. 332 82

Morning plasma corticosterone concentrations have been reported to be elevated in obese Zucker rats compared with lean rats. The aim of this study was to determine if differences in adrenal sensitivity or maximal responsiveness to adrenocorticotropic hormone (ACTH)-(1-24) could account for this disparity. Serum and adrenal glands were collected from lean and obese, male and female Zucker rats (10-13 wk old) between 10:00 and 11:00 A.M. Adrenocortical cells were isolated and challenged with ACTH-(1-24). The serum corticosterone and ACTH concentrations were significantly greater in obese males compared with lean males (45.3 +/- 10.3 vs. 23.2 +/- 1.45 ng/ml and 156.6 +/- 15.3 vs. 113.3 +/- 9.4 pg/ml, respectively). Although serum corticosterone concentrations were similar in female rats, serum ACTH concentrations tended (P = 0.07) to be lower in obese female rats than in lean female rats (67.6 +/- 9.3 vs. 103.5 +/- 15.1 pg/ml, respectively). The median effective concentration (EC50) and the maximal corticosterone response per microgram of DNA of dose-response curves derived from lean and obese rats were not significantly different. Additionally, a morphometric evaluation of adrenal tissue from lean and obese rats suggested that cells of the zona glomerulosa were smaller in obese rats than in lean rats. Our data confirm that morning serum corticosterone concentrations are elevated in 10- to 13-wk-old male Zucker rats. This difference does not appear to be due to differences in the sensitivity or maximal secreting capacity of adrenocortical cells to ACTH.
 ...
PMID:Responsiveness of isolated adrenocortical cells from lean and obese Zucker rats to ACTH. 342 23

The pro-opiomelanocortin (POMC) gene is specifically expressed in corticotroph cells of the anterior pituitary. To define the POMC promoter sequences responsible for tissue-specific expression, we assessed POMC promoter activity by gene transfer into POMC-expressing pituitary tumor cells (AtT-20) and fibroblast L cells. The rat POMC promoter was only efficiently utilized and correctly transcribed in AtT-20 cells. 5'-End deletion analysis revealed two promoter regions required for activity in AtT-20 cells. When tested by fusion to a heterologous promoter, DNA fragments corresponding to both regions exhibited tissue-specific activity, suggesting the presence of at least two tissue-specific DNA sequence elements within the promoter. In summary, POMC promoter sequences from -480 to -34 base pairs appear sufficient to mimic the specificity of anterior pituitary expression.
 ...
PMID:Tissue-specific activity of the pro-opiomelanocortin gene promoter. 343 49

The primary structure of the precursor of urotensin I, a neuropeptide hormone from the caudal neurosecretory system of the carp Cyprinus carpio, has been determined by analyzing the nucleotide sequence of cloned DNA complementary to the mRNA encoding it. The precursor consists of 145 amino acid residues and the carboxyl terminus represents the 41-amino acid sequence of urotensin I, preceded by Lys-Arg and followed by Gly-Lys. Sequence homology as well as similar organization of the precursors of urotensin I and mammalian corticotropin-releasing factors suggest that they are evolutionarily related. RNA transfer blot analysis indicates that mRNA encoding the precursor of urotensin I is present only in the spinal cord and not in the brain, intestine, liver, or kidney of the carp.
 ...
PMID:Cloning and sequence analysis of cDNA encoding urotensin I precursor. 348 50

Proopiomelanocortin (POMC) peptide secretion from rat anterior pituitary corticotrophs and intermediate pituitary melanotrophs is stimulated by corticotropin-releasing hormone (CRH). CRH-stimulated secretion in the corticotrophs is inhibited by glucocorticoids in a complex fashion, involving both a fast, direct blockade of POMC secretion (minutes to hours) and a longer inhibitory action (hours to days) that decreases the amount of POMC peptide available for release. The current studies tested the ability of CRH to stimulate beta-endorphin (a peptide derived from POMC) secretion and POMC gene transcription in cultured anterior and neurointermediate lobe pituitary cells, and examined interactions between CRH and glucocorticoids in regulating POMC gene expression using an in vitro nuclear transcription run-on assay. In both tissues, CRH elicited a time-dependent stimulation of POMC gene transcription that was maximal at 60 min and remained elevated for at least 18 hr. Glucocorticoids rapidly inhibited POMC gene transcription fourfold in the anterior lobe with maximal effects within 20 min. Glucocorticoids also blocked CRH-stimulated POMC gene transcription in anterior pituitary cultures in a temporal manner paralleling their inhibitory effects on CRH-stimulated beta-endorphin secretion. In neurointermediate lobe cultures, the effects of glucocorticoids and CRH on POMC gene transcription were qualitatively similar to, but of lesser magnitude than those observed in the anterior lobe. These studies indicate that the regulation of POMC gene transcription by glucocorticoids and CRH is complex and that the two modulators do not function independently.
DNA 1987 Oct
PMID:Complex transcriptional regulation by glucocorticoids and corticotropin-releasing hormone of proopiomelanocortin gene expression in rat pituitary cultures. 350 23

The GABAergic regulation of proopiomelanocortin messenger RNA (POMC mRNA) levels in rat pituitary was investigated using molecular hybridization of DNA complementary to POMC mRNA. Endogenous GABA levels increased, in vivo, by inhibiting the GABA catabolic enzyme GABA-transaminase (GAT) with ethalonamine-O-sulfate (EOS) or with vinyl-GABA (VG). Rats were treated with VG (100 mg/kg or 800 mg/kg) or EOS (100 mg/kg), administered each second day. GABA levels in the neurointermediate lobe (NIL) and anterior lobe (AL) of the hypophysis and in the hypothalamus were significantly increased following 4 days of VG treatment (800 mg/kg). All treatments resulted in a 40-60% decrease in POMC mRNA levels after 4 days in the NIL but not in the AL. A similar decrease of about 60% in POMC mRNA levels in the NIL was seen when EOS was given in the drinking water (5 mg/ml). In this set of experiments the time course of alteration of POMC mRNA in the NIL and the concentration of alpha-MSH, a POMC-derived peptide, were analysed. After one day of EOS treatment, when POMC levels had already decreased by 40%, alpha-MSH levels were significantly elevated (34% above controls), possibly reflecting an inhibition of alpha-MSH secretion. However, after 4 and 8 days, POMC mRNA levels and tissue alpha-MSH levels had significantly decreased. When tested in vitro, on primary cultures of IL cells, GABA (10 microM) reduced POMC mRNA levels by 40% after 3 days of treatment. These results show that GABA exerts a direct inhibitory effect on POMC gene expression in the intermediate lobe.
 ...
PMID:GABA differentially regulates the gene expression of proopiomelanocortin in rat intermediate and anterior pituitary. 373 46

Total RNA has been prepared from human leukocytes from patients with chronic lymphoblastic leukemia (CLL) as well as from post mortem human caudate nucleus, hypothalamus, cerebellum and cerebral cortex. Dot-blot and Northern blot analysis, using a human proenkephalin A clone and SP-6 derived "complementary" proenkephalin A RNA respectively, revealed the existence of proenkephalin A-like RNA:s in CLL-leukocytes with the same characteristics as in caudate nucleus, hypothalamus, and cortex. Furthermore, RIA and Western blot analysis confirmed that immunoreactive pro-enkephalin A activity is present in human CLL-leukocytes. The progress in DNA recombinant technology has allowed the study of opioid peptide regulation at the transcriptional and translational-posttranslational level. Studies on the distribution and quantitation of preproenkephalin A mRNA in bovine, rat and human central nervous system (CNS) have recently been reported. Different opioid peptides, related to the enkephalins, dynorphins and beta-endorphin have also been detected in tissues outside the CNS including the adrenal medulla and in pheochromocytomas. Northern blot analysis and cDNA-cloning confirmed that the proenkephalin A gene is indeed expressed in these tissues. Proenkephalin A derived peptides are potentially significant in nervous disorders. We have chosen to investigate whether the corresponding gene is expressed not only in CNS-tissues but also in human leukocytes, cells readily obtained in individual patients.
 ...
PMID:Proenkephalin A-like mRNA in human leukemia leukocytes and CNS-tissues. 378 78

We have characterized a precursor protein which gives rise to the neuropeptide Phe-Met-Arg-Phe-amide (FMRFamide) by determining the nucleotide sequence of a genomic and five cDNA clones. The 597-amino-acid protein contains 28 copies of the tetrapeptide FMRFamide, a single Phe-Leu-Arg-Phe-amide (FLRFamide), and other sequences flanked by paired basic residues, some of which have homologies to mammalian brain peptides. The data presented suggest the genes encoding pro-opiomelanocortin, pre-pro-enkephalin, and the hypothalamic releasing factor, cortico-releasing factor (CRF), arose from a common ancestral gene.
DNA 1986 Dec
PMID:The Aplysia FMRFamide gene encodes sequences related to mammalian brain peptides. 381 95


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>