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)

The NH2-terminal domain of pro-opiomelanocortin, designated as the 16-kDa fragment, is highly conserved throughout the vertebrate family and is likely therefore to have an important functional role. Bovine 16-kDa fragment is a 77- residue glycopeptide, which has been found to be glycosylated at threonine 45 and asparagine 65. Available evidence suggests that glycoforms lacking glycans at the O-linked site are processed in the intermediate pituitary at -Arg49-Lys50- to give the residue 1-49 amino-terminal peptide and a carboxyl-terminal glycopeptide referred to as Lys1 gamma 3-melanotropin. Glycoforms carrying O-glycans remain unprocessed in the intermediate pituitary. Thus O-glycosylation is likely to play an important role in controlling the fate of the NH2-terminal portion of pro-opiomelanocortin, thereby affecting the biological events that are influenced by peptides and glycopeptides derived from this domain. In a recent study (Siciliano, R. A., Morris, H. R., McDowell, R. A., Azadi, P., Rogers, M. E., Bennett, H. P. J., and Dell, A. (1993) Glycobiology 3, 225-239), we sequenced the N-glycans attached to Asn-65 of bovine 16-kDa fragment and demonstrated that the acidic components contain, in addition to neutral antennae, a single SO4-4GalNAc beta 1-4GlcNAc beta 1- antenna, which is characteristic of the pituitary glycohormone N-glycans (Baenziger, J. U., and Green, E. D. (1988) Biochim. Biophys. Acta 947, 287-306). We now report the structural characterization of the O-linked oligosaccharides found in bovine 16-kDa fragment. The major component, which constitutes about 80% of the O-glycan population, is a novel sulfated tetrasaccharide, which carries the same sulfated epitope as the N-glycans. This is the first time that the SO4-4GalNAc beta 1-4GlcNAc beta 1- moiety has been observed in O-glycans, and it raises the interesting possibility that the beta-N-acetylgalactosaminyltransferase responsible for the addition of N-acetylgalactosamine to the pituitary glycohormones (Smith, P. L., and Baenziger, J. U. (1988) Science, 242, 930-933) might be capable of glycosylating both N- and O-linked acceptors.
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PMID:O-glycosylation mimics N-glycosylation in the 16-kDa fragment of bovine pro-opiomelanocortin. The major O-glycan attached to Thr-45 carries SO4-4GalNAc beta 1-4GlcNAc beta 1-, which is the archetypal non-reducing epitope in the N-glycans of pituitary glycohormones. 750 11

It has been shown that 1 h restraint shortens pentobarbital (PbNa)-induced sleeping time and that brain corticotropin-releasing hormone (CRH) is involved in the mechanism by which restraint shortens. PbNa-induced sleeping time. The present study was designed to further examine the mechanism of the antagonistic effect of 1 h restraint on PbNa in rats. Intracerebroventricular (i.c.v.) administration of propranolol and metoprolol, but not butoxamine reversed the shortening of PbNa-induced sleeping time by 1 h restraint. The i.c.v. administration of phentolamine blocked the shortening of PbNa-induced sleeping time by restraint, while the same dose of phentolamine prolonged the sleeping time in unrestrained rats. Atropine did not affect the PbNa-induced sleeping time in restrained rats. These results suggest that in addition to CRH, the brain beta 1-adrenergic system is involved in the restraint stress-induced increase in arousal.
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PMID:Beta 1-adrenergic mechanism is involved in stress-induced increase in arousal. 770 May 73

The mechanisms that control lipolysis in intra-abdominal fat cells from various primate species, the marmoset (Callithrix jacchus), the baboon (Papio papio), and the macaque (Macaca fascicularis), were compared to those of human intraabdominal fat cells. Selective beta 1- or beta 2-adrenoceptor agonists induced lipolysis in all species. Selective beta 3-agonists (BRL 37344, CL 316243, and SR 58611) acted as partial agonists in marmoset but were inefficient in other primates, including humans. alpha 2-Adrenoceptor number ([3H]RX 8210002 binding) equalized (baboon) or exceeded (other primates) beta 1/beta 2-adrenoceptors ([3H]CGP 12177 binding). Baboon fat cell membranes expressed similar amounts of coupled beta- and alpha 2-adrenoceptors. In all species, norepinephrine- or epinephrine-induced lipolysis did not reach the lipolytic effect of isoproterenol but their effects were enhanced after alpha 2-adrenoceptor blockade. N6-phenylisopropyladenosine (PIA) induced a full antilipolytic effect in baboon, macaque, and human adipocytes through adenosine receptors ([3H]DPCPX binding). Peptide YY (PYY) weakly inhibited lipolysis in baboon. Adrenocorticotropic hormone (ACTH) was inactive whereas parathyroid hormone (PTH) partially stimulated lipolysis in primates. Histamine was partially lipolytic in marmoset only. This study emphasizes the similarities of the mechanisms controlling the lipolysis in nonhuman primate and in human adipocytes and suggests that the baboon and the macaque should provide unique models for the study of the regulation of lipolysis.
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PMID:Control of lipolysis in intra-abdominal fat cells of nonhuman primates: comparison with humans. 777 57

Differential expression of glycosyltransferases has the potential to generate functionally distinct glycoforms of otherwise identical proteins. We have previously demonstrated the presence of unique oligosaccharides terminating with GalNAc-4-SO4 on the pituitary glycoproteins lutropin (LH), thyroid stimulating hormone (TSH), and pro-opiomelanocortin (POMC). A glycoprotein hormone:GalNAc-transferase and a GalNAc-4-sulfotransferase are present in the pituitary and can account for the synthesis of these unique oligosaccharides on specific glycoproteins. Both transferases are coordinately expressed in a number of tissues in addition to pituitary, including submaxillary gland, lacrimal gland, and kidney, suggesting that additional glycoproteins bearing oligosaccharides terminating with GalNAc-4-SO4 are synthesized in these tissues. In this study we show that while the glycoprotein hormone:GalNAc-transferase and the GalNAc-4-sulfotransferase are coordinately expressed in bovine submaxillary gland, the GalNAc-transferase is expressed in the parotid gland in the absence of the GalNAc-4-sulfotransferase. The relative expression of these two transferases in submaxillary and parotid glands correlates with the presence of unique Asn-linked oligosaccharides on carbonic anhydrase VI (CA VI) synthesized in each of these tissues. The majority of Asn-linked oligosaccharides on CA VI synthesized in submaxillary gland terminate with GalNAc-4-SO4. In contrast, CA VI which is synthesized in bovine parotid gland bears oligosaccharides which terminate predominantly with beta 1,4-linked GalNAc which is not sulfated. The presence of different terminal residues on the Asn-linked oligosaccharides of submaxillary and parotid CA VI thus correlates with the complement of transferases in these glands and suggests differing biological roles for submaxillary and parotid CA VI.
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PMID:Differential expression of GalNAc-4-sulfotransferase and GalNAc-transferase results in distinct glycoforms of carbonic anhydrase VI in parotid and submaxillary glands. 789 Jul 28

Using cultured human fetal adrenal cells, we have investigated the basal secretion of cortisol and dehydroepiandrosterone sulfate (DHAS) and the effect of corticotropin (ACTH), angiotensin-II (A-II) and transforming growth factor beta 1 (TGF beta 1) on the secretion of these steroids and on the mRNA levels of ACTH receptor (ACTHR), cytochrome P-450scc (cholesterol side-chain cleavage), P450 17 alpha (17 alpha-hydroxylase/17-20 lyase) and 3 beta-HSD (3 beta-hydroxysteroid dehydrogenase). The basal DHAS/cortisol ratio declined progressively between 12.5 and 21 weeks. ACTH treatment enhanced the secretion of cortisol and to a lesser extent that of DHAS, and increased the steroidogenic response to an acute stimulation with ACTH. These changes were associated with increased mRNA levels of ACTHR and of the steroidogenic enzymes. A-II treatment also increased the secretion of both DHAS and cortisol, but less than ACTH, enhanced the responsiveness to ACTH and increased ACTHR, P450scc and P450 17 alpha mRNA levels. In contrast, TGF beta 1 alone or together with ACTH decreased DHAS secretion, but not cortisol secretion. Moreover, TGF beta 1 had no effect on ACTHR and P450scc mRNA levels, decreased by about 50% the mRNA levels of P450 17 alpha both in the absence or presence of ACTH, but enhanced the stimulatory effects of ACTH on 3 beta-HSD mRNA. These results, along with those previously reported, suggest that both A-II and TGF beta may play a role in fetal adrenal function. In addition, they show that the effects of both peptides are qualitatively different from, even sometimes opposite to, those previously reported in bovine and ovine adrenal cells.
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PMID:Regulation of corticotropin and steroidogenic enzyme mRNAs in human fetal adrenal cells by corticotropin, angiotensin-II and transforming growth factor beta 1. 789 1

Adrenal cell-differentiated functions and, therefore, their steroidogenic capacity can be regulated in an opposite direction by insulin-like growth factor I (IGF-I) and transforming growth factor-beta 1 (TGF beta 1). The enhanced steroidogenic responsiveness of bovine and ovine adrenal cells treated with IGF-I can be explained by its positive effects on the number of corticotropin (ACTH) and angiotensin II (A-II) receptors associated with an increase in the alpha s and alpha i subunits of G proteins but also by its effects on several steps of the steroidogenic pathway. In contrast, TGF beta 1 is a potent inhibitor of differentiated functions of both bovine and ovine adrenal cells. TGF beta 1 reduces ACTH and A-II receptor number, inhibits cAMP formation, and decreases several steroidogenic enzyme activities. The physiological role of these peptides in adrenal cells is strengthened by the fact that both are synthetized and secreted by these cells and that their secretion can be regulated by the specific hormones, ACTH and A-II.
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PMID:Regulation of adrenal cell-differentiated functions by growth factors. 795 33

alpha-Melanocyte-stimulating hormone (alpha-MSH1-13) and its COOH-terminal tripeptide alpha-MSH11-13 (Lys Pro Val) inhibit inflammation when administered systemically. Recent evidence indicates that alpha-MSH1-13 can likewise inhibit inflammation in the skin solely via an action within the brain. Because of the potential importance of this discovery to understanding the control of inflammation and because alpha-MSH molecules might be useful for treatment of inflammation, experiments were performed to learn more about the mechanisms of action of these peptides. In tests on inflammation induced in the mouse ear by intradermal injections of recombinant human interleukin-1 beta, alpha-MSH1-1-13 administered intracerebroventricularly effectively reduced inflammation. This effect of centrally administered alpha-MSH1-13 was inhibited by systemic injection of the nonspecific beta-adrenergic receptor blocker propranolol and by administration of a specific beta 2-adrenergic receptor antagonist; the effect was not altered by blockade of cholinergic, alpha-adrenergic, or beta 1-adrenergic receptors. In mice with inflammation induced in a hind paw and with the spinal cord transected, the antiinflammatory effect of centrally administered alpha-MSH1-13 was prevented, indicating that intact descending neuronal pathways are required for the antiinflammatory influence of the central peptide. Systemic injection of alpha-MSH1-13 in animals with spinal cord transection had a smaller and later antiinflammatory effect, which suggests that the molecule also has an action, albeit lesser, in the periphery. However, alpha-MSH11-13 injected intraperitoneally had marked antiinflammatory activity in animals with spinal cord transection.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Antiinflammatory influences of alpha-MSH molecules: central neurogenic and peripheral actions. 815 74

Asn-linked oligosaccharides terminating with the sequence SO4-4GalNAc beta 1,4GlcNAc beta 1,2Man alpha (S4GGnM) are present on the glycoprotein hormones lutropin and thyrotropin, pro-opiomelanocortin, and tissue factor pathway inhibitor. The peptide motif ProXaaArg/Lys (PXR/K), which is recognized by a PXR/K-specific GalNAc-transferase, is present in each of these glycoproteins 6-9 residues NH2-terminal to an Asn glycosylation site. Both the PXR/K-specific GalNAc-transferase and a GalNAc beta 1,4GlcNAc beta 1,2Man alpha (GGnM)-4-sulfotransferase are required for synthesis of the S4GGnM sequence. Glycoproteins which do not contain the PXR/K motif but bear Asn-linked oligosaccharides terminating with GGnM or sialic acid alpha 2,3/6GGnM have also been described, suggesting a distinct GalNAc-transferase may be responsible for their synthesis. We have examined a number of tissues and cultured cell lines for the transfer of sulfate to the trisaccharide acceptor GGnM and transfer of GalNAc to oligosaccharide acceptors on protein which do, human chorionic gonadotropin (hCG), and do not, transferrin (Trf), contain the PXR/K motif. The PXR/K-specific GalNAc-transferase and the GGnM-4-sulfo-transferase are expressed in salivary gland, pituitary, lacrimal gland, kidney, and brain, and in the cell lines AtT-20, 293, SHSY5Y, and alpha T3. In contrast Bowes, EL-4, and B16L6 cell extracts transferred GalNAc to oligosaccharides acceptors on Trf but not on hCG. A number of tissues and cell lines displayed transfer of GalNAc to both hCG and to Trf suggesting that two distinct GalNAc-transferases were present. The GGnM-4-sulfotransferase was expressed in tissues and cell lines which expressed the PXR/K-specific GalNAc-transferase but not in cell lines expressing exclusively the Trf-specific GalNAc-transferase. Thus, the PXR/K-specific GalNAc-transferase and the GGnM-4-sulfotransferase are coordinately expressed in a number of tissues other than pituitary. The Trf-specific GalNAc-transferase may account for the presence of beta 1,4-linked GalNAc on glycoproteins which do not contain the PXR/K motif.
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PMID:Co-ordinate and restricted expression of the ProXaaArg/Lys-specific GalNAc-transferase and the GalNAc beta 1,4GlcNAc beta 1,2Man alpha-4-sulfotransferase. 834 98

Using cultured bovine adrenal fasciculata cells (BAC), we investigated the effects of two hormones, corticotropin (ACTH) and angiotensin II (Ang-II) and two growth factors, insulin-like growth factors I (IGF-I) and transforming growth factor beta 1 (TGF beta 1), on the mRNA levels of nuclear proto-oncogenes of the Fos and Jun families and on the mRNA levels of genes expressed in BAC coding for ACTH and AT1 receptors, cytochrome P450scc and P450 17 alpha and 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD). ACTH and IGF-1 increased c-fos and jun-B mRNA levels early with later increases in the levels of mRNA for the ACTH receptor and the three steroidogenic enzymes, and enhanced steroidogenic responses to both ACTH and Ang-II. In contrast, Ang-II increased mRNA coding for the three proto-oncogenes (cfos, c-jun, and jun-B), decreased those for P450 17 alpha and 3 beta-HSD, and caused marked homologous and heterologous steroidogenic desensitization. TGF beta 1 increased only jun-B mRNA and markedly reduced BAC-differentiated functions and steroidogenic responsiveness to both ACTH and Ang-II. The long-term effects of ACTH on human adrenal fasciculata cells were comparable with those observed in BAC, whereas the long term effects of Ang-II and TGF beta 1 were different from those observed in BAC. Whether these species-specific differences are related to a different effect of these factors on proto-oncogene expression is not yet known.
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PMID:Regulation of primary response and specific genes in adrenal cells by peptide hormones and growth factors. 873 96

In the Alzheimer disease (AD) brain, senile plaques contain several proteins and cytokines, such as beta-amyloid protein (A beta), interleukin 1, transforming growth factor beta 1 (TGF beta 1), and apolipoprotein E, which may contribute to the process of neurodegeneration. Clusterin is also known to colocalize with A beta deposits in neuritic plaques. Clusterin is a multifunctional protein that causes cell aggregation, binds to beta-endorphin, and inhibits the terminal complex formation of complement. Clusterin mRNA and protein are increased in the brains of AD patients. Cytokines such as TGF beta 1 and interleukin 1 enhance the expression of clusterin, which may link clusterin to inflammatory mechanisms in AD. A beta, a 39-43 amino acid peptide, is a major component of the senile plaques that are characteristic of AD. Highly aggregated A beta is implicated in neurodegeneration, e.g., A beta aggregates spontaneously into fibrillar forms resembling those in plaques that, in experimental models, cause neurotoxicity through oxidative stress. Clusterin inhibits the aggregation of A beta, which might be neuroprotective according to the aggregation-toxicity hypothesis of A beta. However, clusterin enhanced the oxidative stress of A beta. This may extend its neurotoxicity to locations distal from plaques wherever A beta is present.
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PMID:Relationship between multifunctional protein "clusterin" and Alzheimer disease. 889 44


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