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)

Intracellular proteolytic processing of fusion glycoprotein precursors (F0) of paramyxoviruses, i.e. a virulent strain of Newcastle disease virus (NDV), parainfluenza virus type 3 (PIV3) and simian virus 5 (SV5), was examined in NALM6 and BSC40 cells and compared with that in LLCMK2 cells to investigate the distribution of the virus-activating protease(s) among the cells and its substrate specificity. BSC40 cells lack a processing endoprotease of the neuropeptide precursor, pro-opiomelanocortin (POMC), which possesses multiple cleavage sites at pairs of basic residues, Lys-Arg and Arg-Arg, a motif similar to that found in the cleavage site of the F0 proteins. In NALM6 cells, only small amounts of the F0 protein of virulent NDV was cleaved whereas those of PIV3 and SV5 were efficiently cleaved. In BSC40 cells the F0 proteins of these three viruses were cleaved normally as well as in LLCMK2 cells. The processing inhibitors monensin, chloroquine and A23187 suppressed the F0 cleavage in the three cell types. These results indicate that both NALM6 and BSC40 cells possess virus-activating proteases similar to that of LLCMK2 cells, but suggest that the enzyme of NALM6 may be slightly different in its substrate specificity from those of BSC40 and LLCMK2. The results also suggest that the virus-activating proteases are different in their distribution and substrate specificity from the processing enzyme of POMC.
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PMID:Distribution and substrate specificity of intracellular proteolytic processing enzyme(s) for paramyxovirus fusion glycoproteins. 131 18

Evidence has accumulated that human peripheral blood mononuclear cells (PBMC) may release adrenocorticotropic hormone (ACTH) and endorphin-like peptides into the culture medium when stimulated with different substances such as Newcastle disease virus and the lipopolysaccharide of Escherichia coli. However, to our knowledge, no quantitative assessment of ACTH-LIR (like-immunoreactivity) in human PBMC has been reported. We thus utilized a radioimmunoassay for ACTH to find a median of 30 pg of ACTH-LIR in 10(7) PBMC of 11 normal subjects. ACTH-LIR was also detected in 7 different cell lines derived from patients with lymphoid and myeloid malignancies, two of them, JM and U937, showed values of 135 and 108 pg/10(7) cells respectively. Stimulation with IL-1 beta at the concentration of 1000 U/mL induced, after 48 h, a significant increase of intralymphocytic ACTH levels when compared to basal and 24 h values. The chromatographic characterization of this ACTH-LIR showed, at least, three molecular forms of immunoreactive ACTH; molecular weights were 31 kD POMC, 22 kD ACTH and 4.5 kD ACTH. We used northern blotting with human genomic DNA probe for POMC gene to evidence specific mRNA in PBMC; mRNA was also observed in a T lymphocyte cell line derived from a patient with lymphoma. We conclude that PBMC produce ACTH-LIR which may act as a paracrine immunomodulator similar to lymphokine and/or may signal the adrenal gland to secrete glucocorticoids.
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PMID:[ACTH of lymphocytic origin under normal and pathological conditions]. 166 15

Infection of lymphocytes with Newcastle disease virus induces the cells to synthesize immunoreactive (ir) adrenocorticotropin (ACTH) and endorphins. The irACTH is synthesized de novo, and common properties of lymphocyte and pituitary ACTH include: antigenicity, bioactivity, molecular weight, and retention time on reverse phase high-pressure liquid chromatography. The irACTH appears to be active in vivo because a rise in serum corticosterone levels in hypophysectomized mice corresponds with spleen cell production of irACTH. Furthermore, preliminary experiments showed that B cell depletion blocked the normal rise in serum corticosterone levels after herpes simplex virus infection of intact mice. It seems that a similar system operates in vivo in humans. Typhoid vaccine, which induces lymphocyte-derived irACTH production in vitro, caused a time-dependent increase in the number of irACTH-positive lymphocytes in both hypopituitarism and normal short children. A rise in serum cortisol levels was seen in one patient with hypopituitarism and all normal patients. The above regulatory circuit also seems able to act in the reverse direction. Pituitary ACTH and alpha-endorphin can behave like lymphokines by being immunosuppressive at 0.5 microM in an in vitro antibody synthesis system. Further, lymphocytes were shown to have high-affinity receptors for both of these hormones. Thus, it appears that the immune and neuroendocrine systems have the ability to signal each other through common or related peptide hormones and receptors.
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PMID:A complete regulatory loop between the immune and neuroendocrine systems. 257 15

Infection of murine splenocytes with Newcastle disease virus results in expression of the proopiomelanocortin gene as determined by dot and northern blot analysis of total cellular and poly(A)+ cytoplasmic RNA. These data provide the first evidence that the precursor protein for adrenocorticotropin and beta-endorphin can be synthesized by lymphoid cells.
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PMID:Newcastle disease virus-infected splenocytes express the proopiomelanocortin gene. 287 61

Previous reports have shown that there is an endogenous opioid component associated with pathophysiological responses to endotoxin. It has been shown that these responses are alleviated by naloxone, a specific opiate antagonist. Results of another study have indicated that leukocytes may mediate some of those responses since leukocyte depletion alleviated the effects of lipopolysaccharide. In view of the above reports as well as the finding that leukocytes produce immunoreactive (ir-) endorphins and corticotropin (ACTH) when stimulated with Newcastle disease virus or ACTH-releasing factor, we postulated that leukocytes may serve as an extrapituitary source of endorphins produced in response to bacterial endotoxin. To test this hypothesis, human peripheral blood leukocytes as well as mouse spleen cells were cultured in vitro with Escherichia coli lipopolysaccharide for 48 h. The lipopolysaccharide (i.e., endotoxin) was shown to induce de novo synthesis of ir-ACTH and ir-endorphins. The leukocyte-derived ir-ACTH had a molecular weight of approximately 2,900 and demonstrated a bioactivity similar to that of pituitary-derived ACTH. The lymphocyte-derived ir-endorphin comigrated with alpha- and gamma-endorphin at approximately 1,800 daltons and was shown to bind to brain opiate receptors. These findings imply that leukocyte-derived endorphins may be involved in the pathophysiological response to endotoxin.
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PMID:Bacterial lipopolysaccharide induction of leukocyte-derived corticotropin and endorphins. 298 31

The production and action of immunoregulatory cytokines, including interleukin-1 (IL-1), are inhibited by glucocorticoid hormones in vivo and in vitro. Conversely, glucocorticoid blood levels were increased by factors released by human leukocytes exposed to Newcastle disease virus preparations. This activity was neutralized by an antibody to IL-1. Therefore the capacity of IL-1 to stimulate the pituitary-adrenal axis was tested. Administration of subpyrogenic doses of homogeneous human monocyte-derived IL-1 or the pI 7 form of human recombinant IL-1 to mice and rats increased blood levels of adrenocorticotropic hormone (ACTH) and glucocorticoids. Another monokine, tumor necrosis factor, and the lymphokines IL-2 and gamma-interferon had no such effects when administered in doses equivalent to or higher than those of IL-1. The stimulatory effect of IL-1 on the pituitary-adrenal axis seemed not to be mediated by the secondary release of products from mature T lymphocytes since IL-1 was endocrinologically active when injected into athymic nude mice. These results strongly support the existence of an immunoregulatory feedback circuit in which IL-1 acts as an afferent and glucocorticoid as an efferent hormonal signal.
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PMID:Immunoregulatory feedback between interleukin-1 and glucocorticoid hormones. 301 62

Infection of hypophysectomized mice with Newcastle disease virus caused a time-dependent increase in corticosterone and interferon production. Prior treatment with dexamethasone completely inhibited the virus-induced elevation in corticosterone concentration, but did not significantly alter the interferon response. Lymphocytes appear to be the most likely source of an adrenocorticotropin-like substance that is responsible for the increased corticosterone, since spleen cells from the virus-infected, but not from control or dexamethasone-treated, hypophysectomized mice showed positive immunofluorescence with antibody to adrenocorticotropin-(1-13 amide). Thus the adrenocorticotropin-like material and interferon appear to be coordinately induced the differentially controlled products of different genes. These findings strongly suggest the existence of a lymphoid-adrenal axis.
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PMID:Virus-induced corticosterone in hypophysectomized mice: a possible lymphoid adrenal axis. 618 48

Corticosterone plasma concentration was measured in a random-bred control line and in 3 White Leghorn chicken lines previously selected over 9 generations for 3 different in vivo immune responses: high antibody response to Newcastle disease virus vaccine 3 wk after vaccination (ND3), high cell-mediated immune response (response to phytohemagglutinin, PHA), and high phagocytic activity measured as carbon clearance (CC). The objective of the study was to estimate if selection on immune response had an effect on the response to stress assessed by measures of corticosterone concentration before and after physical stress or adrenocorticotropin hormone injection and if the effect was dependent on the immune response trait that had been selected for, by joint analyses of immune responses and concentrations. The mean values of plasma corticosterone measures did not differ between lines, indicating that selection for different high immune responses had little effect on response to stress. Within line, however, significant negative correlations (-0.46 <or= r <or= -0.39) were found between cell-mediated immunity and corticosterone plasma concentrations in 3 of the 4 lines. Moreover, in the line selected for high antibody titers (ND3-L), corticosterone levels were positively correlated to ND3 (r = 0.41 and 0.47) and negatively correlated to CC (r = -0.48).
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PMID:Circulating corticosterone reaction to restraint and adrenocorticotropin hormone administration in white leghorns selected for immune response traits. 1893 Nov 71