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 excitatory actions of corticotropin-releasing hormone (CRH) in the brain and the neuroprotective effects of CRH antagonists in models of ischemia suggest a role for this peptide in the cascade of events leading to cellular damage. The present study aimed to characterize endogenous activation of CRH in discrete brain regions following global ischemia. Time-dependent changes in CRH concentrations were assessed in 10 brain regions including hippocampal, parahippocampal, and hypothalamic regions as well as the amygdala and the frontal cortex at three post-ischemic intervals: 4, 24, and 72 h (Experiment 1). The impact of pretreatment with a neuroprotective dose of the NMDA antagonist (5R,10S)-(+)-5-Methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine hydrogen maleate (MK-801; hydrogen maleate) on 24-h ischemia-induced CRH concentrations in the 10 brain regions was also determined (Experiment 2). In vivo microdialysis was used to assess dynamic fluctuations in CRH release at the dorsal hippocampus (CA1 pyramidal layer) and central nucleus of the amygdala (CeA; Experiment 3). Our findings revealed a rapid elevation of CRH concentrations at the piriform cortex (Pir) and hypothalamic nuclei following global ischemia. This was followed by decreased CRH concentrations at the amygdala, the frontal cortex (FC), the CA3, and the hypothalamus 24-h post-ischemia. MK-801 reversed the decreases in the hypothalamic nuclei but not in the other brain regions. Seventy-two hours post-ischemia, CRH levels returned to control values in all regions except the dentate gyrus (DG) where elevated CRH levels were observed. In vivo, a significant increase in CRH release in response to global ischemia was found at the CeA with no alterations at the CA1. These findings support brain region-specific ischemia-induced CRH alterations and suggest that CRH actions to mediate neuronal damage at the hippocampal CA1 layer may be indirect.
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PMID:Time-dependent changes in CRH concentrations and release in discrete brain regions following global ischemia: effects of MK-801 pretreatment. 1523 51

Cpe(fat/fat) mice have a point mutation in the coding region of the carboxypeptidase E gene that renders the enzyme inactive. As a result, these mice have reduced levels of several neuropeptides and greatly increased levels of the peptide processing intermediates that contain C-terminal basic residues. However, previous studies examined a relatively small number of neuropeptides. In the present study, we used a quantitative peptidomics approach with stable isotopic labels to examine the levels of pituitary peptides in Cpe(fat/fat) mice relative to wild-type mice. Pituitary extracts from mutant and wild type mice were labeled with the stable isotopic label [3-(2,5-dioxopyrrolidin-1-yloxycarbonyl)propyl]trimethylammonium chloride containing nine atoms of hydrogen or deuterium. Then, the two samples were pooled and analyzed by liquid chromatography/mass spectrometry (LC/MS). The relative abundance of peptides was determined from a comparison of the intensities of the heavy and light peaks. Altogether, 72 peptides were detected in the Cpe(fat/fat) and/or wild-type mouse pituitary extracts of which 53 were identified by MS/MS sequencing. Several peptides identified in this analysis represent previously undescribed post-translational processing products of known pituitary prohormones. Of the 72 peptides detected in pituitary, 17 were detected only in the Cpe(fat/fat) mouse extracts; these represent peptide processing intermediates containing C-terminal basic residues. The peptides common to both Cpe(fat/fat) and wild-type mice were generally present at 2-5-fold lower levels in the Cpe(fat/fat) mouse pituitary extracts, although some peptides were present at equal levels and one peptide (acetyl beta-endorphin 1-31) was increased approximately 7-fold in the Cpe(fat/fat) pituitary extracts. In contrast, acetyl beta-endorphin 1-26 was present at approximately 10-fold lower levels in the Cpe(fat/fat) pituitary, compared with wild-type mice. The finding that many peptides are substantially decreased in Cpe(fat/fat) pituitary is consistent with the broad role for carboxypeptidase E in the biosynthesis of numerous neuropeptides.
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PMID:Relative quantitation of peptides in wild-type and Cpe(fat/fat) mouse pituitary using stable isotopic tags and mass spectrometry. 1570 30

The human skin holds the capacity for autocrine processing of the proopiomelanocortin (POMC)-derived peptides. Recent data demonstrated the presence and functionality of ACTH, alpha- and beta-melanocyte-stimulating hormone (MSH), and beta-endorphin in the regulation of skin pigmentation, and a role has been put forward for alpha-MSH as an effective antioxidant. In patients with vitiligo, decreased epidermal POMC processing and low alpha-MSH levels were documented previously. These patients accumulate hydrogen peroxide (H2O2) in the 10(-3) M range in their epidermis. Therefore, we examined the involvement of H2O2 on POMC-derived peptides as possible targets for oxidation by this reactive oxygen species. To address this, we employed immunofluorescence labelling, dot blot analysis, Fourier transform Raman spectroscopy, functionality studies, and computer simulation of the peptide structures. We demonstrate H2O2-mediated oxidation of epidermal ACTH, alpha-MSH, and beta-endorphin in vitiligo owing to oxidation of methionine residues in the sequences of these peptides. Moreover, we show that oxidized beta-endorphin loses its function in the promotion of pigmentation in melanocytes. These changes are reversible upon the reduction of H2O2 levels by a pseudocatalase PC-KUS. Moreover, oxidation of alpha-MSH can be prevented by the formation of a 1:1 complex with the abundant cofactor (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin. Thus, using vitiligo, we demonstrate that H2O2 can affect pigmentation via epidermal POMC peptide redox homeostasis.
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PMID:Oxidative stress via hydrogen peroxide affects proopiomelanocortin peptides directly in the epidermis of patients with vitiligo. 1694 14

The objective of the present study was to investigate the effect of acute exposure to electric tail shock stress (ES) and a stress witnessing procedure (SW), as models for physical and psychological stress paradigms, respectively on adherence, phagocytosis and hydrogen peroxide (H(2)O(2)) release from rat peritoneal macrophages. In addition, we studied the in vitro effects of corticosterone (CORT), neuropeptide Y (NPY) and beta-endorphin (BE) on adherence, phagocytosis and H(2)O(2) release from macrophages isolated from control rats and from rats that had been exposed to ES or SW procedures 24 h earlier. ES and SW comparably diminished phagocytosis and H(2)O(2) release, but did not influence macrophage adherence. In vitro treatment with CORT and NPY notably suppressed phagocytosis and potentiated H(2)O(2) release from macrophages. BE suppressed both phagocytosis and H(2)O(2) release from macrophages. Previous exposure to ES and SW altered the responsiveness of the isolated macrophages to their in vitro treatment with mediators of stress, making the cells less sensitive to the influence of CORT and NPY and to a lesser extent to BE. It could be concluded that changes in the local macrophage milieu induced by ES and SW 24 h earlier modify macrophage responses to subsequent in vitro exposure to the stress mimics, CORT, NPY and BE.
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PMID:Exposure to acute physical and psychological stress alters the response of rat macrophages to corticosterone, neuropeptide Y and beta-endorphin. 1745 68

N-(2-Nitrophenyl)proline (2-NPP) amides of primary amines have a conformational preference for intramolecular hydrogen bonding. Because of the strong and selective anisotropic effects on the amine substituents, the absolute configuration of alpha-chiral primary amines can be assigned by comparing the 1H chemical shifts of diastereomeric 2-NPP amides.
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PMID:N-(2-Nitrophenyl)proline: an intramolecular hydrogen bond forming reagent for the determination of the absolute configuration of primary amines. 1771 Dec 92

1. Hydrogen sulphide (H(2)S) acts as a gaseous cellular messenger and has recently been reported to induce a suspended animation-like state in mice. The aim of the present study was to investigate the protective role of H(2)S exposure in stress gastric ulcer. 2. In the present study, we used a rat model of water immersion and restraint stress (WRS) to induce the typical stress disease, namely stress gastric ulcer. Rats were treated with WRS for 4 h, with or without pre-exposure to H(2)S (160 p.p.m. H(2)S for 2.5 h). 3. In H(2)S-exposed rats, body temperature was significantly reduced by 2.5C (P < 0.01) and oxygen consumption was reduced by 37.1% (P < 0.01) compared with control rats. Plasma levels of H(2)S were increased by 20.8% (P < 0.01) following pre-exposure. Pre-exposure to H(2)S significantly reduced the gastric ulcer index, from 24 +/- 9 to 9 +/- 2 (P < 0.01), in WRS rats. In addition, WRS increased plasma levels of adrenocorticotropin (ACTH) and corticosterone 4.7- and 4.8-fold, respectively (both P < 0.01). Pre-exposure to H(2)S markedly suppressed plasma ACTH and corticosterone level by 34.4 and 53.2%, respectively (both P < 0.01), and reduced WRS-elevated myeloperoxidase (MPO) activity by 19%. In the present study, WRS increased gastric malondialdehyde and conjugated diene content by 42 and 68%, respectively (both P < 0.01), and H(2)S exposure reduced lipid peroxide production. Finally, H(2)S exposure inhibited the WRS-elevated expression of glucose-regulated protein 78 and caspase 12, markers of endoplasmic reticulum stress. 4. In conclusion, a low concentration of H(2)S may be a new pharmacological tool for induced hypothermia to prevent severe stress-induced diseases and multifarious trauma in the clinical setting.
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PMID:Hydrogen sulphide-induced hypothermia attenuates stress-related ulceration in rats. 1794 93

Cutaneous pigmentation is the major photoprotective mechanism against the carcinogenic and aging effects of UV. Epidermal melanocytes synthesize the pigment melanin, in the form of eumelanin or pheomelanin. Synthesis of the photoprotective eumelanin by human melanocytes is regulated mainly by the melanocortins alpha-melanocortin (alpha-MSH) and adrenocorticotropic hormone (ACTH), which bind the melanocortin 1 receptor (MC1R) and activate the cAMP pathway that is required for UV-induced tanning. Melanocortins stimulate proliferation and melanogenesis and inhibit UV-induced apoptosis of human melanocytes. Importantly, melanocortins reduce the generation of hydrogen peroxide and enhance repair of DNA photoproducts, independently of pigmentation. MC1R is a major contributor to the diversity of human pigmentation and a melanoma susceptibility gene. Certain allelic variants of this gene, namely R151C, R160W and D294H, are strongly associated with red hair phenotype and increased melanoma susceptibility. Natural expression of two of these variants sensitizes melanocytes to the cytotoxic effect of UV, and increases the burden of DNA damage and oxidative stress. We are designing potent melanocortin analogs that mimic the effects of alpha-MSH as a strategy to prevent skin cancer, particularly in individuals who express MC1R genotypes that reduce but do not abolish MC1R function, or mutations in other melanoma susceptibility genes, such as p16.
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PMID:The melanocortin 1 receptor and the UV response of human melanocytes--a shift in paradigm. 1828 87

One skin cancer prevention strategy that we are developing is based on synthesizing and testing melanocortin analogs that reduce and repair DNA damage resulting from exposure to solar ultraviolet (UV) radiation, in addition to stimulating pigmentation. Previously, we reported the effects of tetrapeptide analogs of alpha-melanocortin (alpha-MSH) that were more potent and stable than the physiological alpha-MSH, and mimicked its photoprotective effects against UV-induced DNA damage in human melanocytes. Here, we report on a panel of tripeptide analogs consisting of a modified alpha-MSH core His(6)-d-Phe(7)-Arg(8), which contained different N-capping groups, C-terminal modifications, or arginine mimics. The most potent tripeptides in activating cAMP formation and tyrosinase of human melanocytes were three analogs with C-terminal modifications. The most effective C-terminal tripeptide mimicked alpha-MSH in reducing hydrogen peroxide generation and enhancing nucleotide excision repair following UV irradiation. The effects of these three analogs required functional MC1R, as they were absent in human melanocytes that expressed non-functional receptor. These results demonstrate activation of the MC1R by tripeptide melanocortin analogs. Designing small analogs for topical delivery should prove practical and efficacious for skin cancer prevention.
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PMID:alpha-MSH tripeptide analogs activate the melanocortin 1 receptor and reduce UV-induced DNA damage in human melanocytes. 1971 49

Exposure of cultured human melanocytes to ultraviolet radiation (UV) results in DNA damage. In melanoma, UV-signature mutations resulting from unrepaired photoproducts are rare, suggesting the possible involvement of oxidative DNA damage in melanocyte malignant transformation. Here we present data demonstrating immediate dose-dependent generation of hydrogen peroxide in UV-irradiated melanocytes, which correlated directly with a decrease in catalase activity. Pretreatment of melanocytes with alpha-melanocortin (alpha-MSH) reduced the UV-induced generation of 7,8-dihydro-8-oxyguanine (8-oxodG), a major form of oxidative DNA damage. Pretreatment with alpha-MSH also increased the protein levels of catalase and ferritin. The effect of alpha-MSH on 8-oxodG induction was mediated by activation of the melanocortin 1 receptor (MC1R), as it was absent in melanocytes expressing loss-of-function MC1R, and blocked by concomitant treatment with an analog of agouti signaling protein (ASIP), ASIP-YY. This study provides unequivocal evidence for induction of oxidative DNA damage by UV in human melanocytes and reduction of this damage by alpha-MSH. Our data unravel some mechanisms by which alpha-MSH protects melanocytes from oxidative DNA damage, which partially explain the strong association of loss-of-function MC1R with melanoma.
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PMID:alpha-MSH activates immediate defense responses to UV-induced oxidative stress in human melanocytes. 1965 42

In order to define the structural requirements of quinazoline-2(1H)-thiones 1 for their inhibitory activity on melanogenesis, a novel series of 3,4-dihydroquinazoline-2(1H)-thiones (3a-h) were prepared and screened for their melanogenesis inhibition on melanoma B16 cell line under the stimulant of alpha-MSH. The anti-melanogenesis activity of 3 is mainly mediated by the hydrogen bonding ability of thioamide unit in addition to complexation ability of thione and the hydrophobic binding power of side chain substitutions at 3-position. Thus, the pharmacophore of 3,4-dihydroquinazoline-2(1H)-thiones for their anti-melanogenesis activity could be refined as 3-hydrophobic substituted quinazolinethione.
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PMID:Refinement of the pharmacophore of 3,4-dihydroquinazoline-2(1H)-thiones for their anti-melanogenesis activity. 2063 80


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