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)

Adaptation of the adrenal gland to the demands of the organism is regulated functionally and structurally. Three common hypotheses on zonation in the adrenal gland, the migrational, zonal, and transformation field theories, try independently to reconcile the findings on structure, proliferation, and cell death. The classical theories on zonation are revisited in the light of recent data on cell death and renewal. In accordance with data on cell death as immunoreactivity against FAS(CD 95), an apoptosis-inducing receptor, in situ end labelling of fragmented DNA, and ultrastructural analyses, programmed cell death (PCD) occurs throughout the whole organ. The angiotensin II receptor subtypes described in the adrenal allow an additional regulation of tissue homeostasis by proliferative and even by the antiproliferative effects of the angiotensin II type 2 receptor. Proto-oncogenes are involved in the regulation of cell cycle and PCD, and adrenocorticotropin asserts its tissue integrating and differentiating effects by regulating proto-oncogenes such as c-jun, c-fos, jun-B and c-myc. Polypeptides involved in proliferation and DNA repair, such as proliferating cell nuclear antigen and Ki-67, have been found within zones of expected cell senescence. The expression of the class II major histocompatibility complex on normal adrenocortical cells allows cell-to-cell communication with the immune system and may trigger the Fas/Fas-ligand system to permit tissue regression and decreasing activity in both systems. In summary, new data allow us to reappraise and to reconcile the classical theories. Apoptosis is a physiological process in the adrenal gland. There is a differential regulation of apoptosis in the different zones. An investigation of this process may elucidate the basic mechanisms of adrenal zonation.
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PMID:Tissue remodelling in the adrenal gland. 969 69

We have previously shown that corticotropin-releasing hormone plays an important proinflammatory role in the induction of experimental autoimmune uveoretinitis. In this study, we examined the role of apoptosis in the destruction of the retina during experimental autoimmune uveoretinitis, and the role of corticotropin-releasing hormone as a local regulator of Fas and Fas Ligand expression in this condition. We evaluated apoptosis by the terminal deoxynucleotidyl transferase dUTP nick end labeling method and Fas and Fas Ligand presence by immunohistochemistry. We examined formalin-fixed, paraffin-embedded eye sections from female Lewis rats or B10.A mice immunized with the major pathogenetic epitope (R16 peptide) of the interphotoreceptor retinoid-binding protein. Female B10.A mice similarly immunized were treated with intraperitoneal injections of the rabbit anti-corticotropin-releasing hormone antibody TS-2 or nonimmune rabbit serum. The percentage of retinal cells undergoing apoptosis and the expression of Fas and Fas Ligand were increased in inflamed retinas in immunized Lewis rats and B10.A mice, compared to controls. Retinas from immunized B10.A mice treated with anti-corticotropin-releasing hormone antibody showed significantly lower apoptosis and Fas and Fas Ligand expression than placebo-treated animals. In conclusion, retinal cells in experimental autoimmune uveoretinitis undergo apoptosis associated with concurrent upregulation of Fas and Fas Ligand. The local presence of corticotropin-releasing hormone appears to be of pivotal importance in this process.
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PMID:Fas/Fas ligand-associated apoptosis in experimental autoimmune uveoretinitis in rodents: role of proinflammatory corticotropin-releasing hormone. 1138 50

The pathogenesis of chronic cyclosporine A (CsA) nephrotoxicity has not been elucidated, but apoptosis is thought to play an important role in CsA induced tubular atrophy. Recently Fas-Fas ligand system mediated apoptosis has been frequently reported in many epithelial cells as well as in T lymphocytes. We investigated the ability of CsA to induce apoptosis in cultured human proximal tubular epithelial cells and also the effect of alpha-MSH on them. Fas, Fas ligand, and an intracellular adaptor protein, Fas-associating protein with death domain (FADD) expression, and poly-ADP ribose polymerase (PARP) cleavage were also studied. CsA induced apoptosis in cultured tubular epithelial cells demonstrated by increased number of TUNEL positive cells and it was accompanied by a significant increase in Fas mRNA and Fas ligand protein expressions. FADD and the cleavage product of PARP also increased, indicating the activation of caspase. In alpha-MSH co-treated cells, apoptosis markedly decreased with downregulation of Fas, Fas ligand and FADD expressions and also the cleavage product of PARP. In conclusion, these data suggest that tubular cell apoptosis mediated by Fas system may play a role in tubular atrophy in chronic CsA nephrotoxicity and pretreatment of alpha-MSH may have a some inhibitory effect on CsA induced tubular cell apoptosis.
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PMID:alpha-Melanocyte stimulating hormone (MSH) decreases cyclosporine a induced apoptosis in cultured human proximal tubular cells. 1164 30

Recent experimental findings involve corticotropin-releasing hormone (CRH) in the cellular response to noxious stimuli and possibly apoptosis. The aim of the present work was to examine the effect of CRH on apoptosis and the Fas/Fas ligand system in an in vitro model, the PC12 rat pheochromocytoma cell line, which is widely used in the study of apoptosis and at the same time expresses the CRH/CRH receptor system. We have found the following. CRH induced Fas ligand production and apoptosis. These effects were mediated by the CRH type 1 receptor because its antagonist antalarmin blocked CRH-induced apoptosis and Fas ligand expression. CRH activated p38 mitogen-activated protein kinase, which was found to be essential for CRH-induced apoptosis and Fas ligand production. CRH also promoted a rapid and transient activation of ERK1/2, which, however, was not necessary for either CRH-induced apoptosis or Fas ligand production. Thus, CRH promotes PC12 apoptosis via the CRH type 1 receptor, which induces Fas ligand production via activation of p38.
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PMID:Corticotropin-releasing hormone induces Fas ligand production and apoptosis in PC12 cells via activation of p38 mitogen-activated protein kinase. 1179 Jul 88

Corticotropin-releasing hormone (CRH) is distributed in the brain and spinal cord and it has also been found in the myometrium, the endometrium, the placenta and diverse inflammatory sites. Traditionally, hypothalamic CRH has been considered to act indirectly in an anti-inflammatory fashion, since the end product of the hypothalamic-pituitary-adrenal axis is cortisol, a well-known anti-inflammatory compound. However, CRH produced at peripheral inflammatory sites may participate in an auto-/paracrine stimulation of inflammation. CRH in inflammatory sites seems to be involved in the activation of the Fas/Fas ligand system. Furthermore, locally produced embryonic and endometrial CRH plays a role in both the aseptic inflammatory process of implantation and the anti-rejection process that protects the fetus from the maternal immune system. There are two types of G protein-coupled CRH receptors, type 1 and 2. Pyrrolopyrimidine compounds, such as antalarmin, have been developed as CRH receptor antagonists. The systemic administration of antalarmin blocks pituitary CRH receptors and the CRH-induced secretion of adrenocorticotropin. Additonally, antalarmin has been shown to reduce the inflammatory-like reaction of the endometrium to the invading blastocyst, with a possible therapeutic potential as a non-steroidal inhibitor of pregnancy at its early stages.
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PMID:The emerging role of peripheral corticotropin-releasing hormone (CRH). 1284 46

Epithelial cells of human endometrium and differentiated endometrial stromal cells express the corticotropin-releasing hormone (CRH) gene. CRH is also produced by the human placental cytotrophoblast. Endometrial and placental CRH is under the endocrine control of gonadal steroids as well as under an autocrine/paracrine regulation by prostanoids and interleukins. Human endometrium, myometrium and placenta also express the relevant receptors. Invasive trophoblasts promote apoptosis of activated Fas-expressing human T lymphocytes, an effect potentiated by CRH and inhibited by the CRH type 1 antagonist, antalarmin. Female rats treated with antalarmin during the first 6 days of gestation had a dose-dependent decrease of implantation sites and live embryos, and significantly decreased endometrial FasL expression. Our data suggest important physiological roles of endometrial and placental CRH in the regulation of decidualization, blastocyst implantation, and early maternal tolerance.
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PMID:Uterine and embryonic trophoblast CRH promotes implantation and maintenance of early pregnancy. 1464 13

Recently, liver natural killer T (NKT) cells, which are specifically stimulated by alpha-galactosylceramide (alpha-GalCer), were found to play a critical role in intrahepatic immunity to several infections and certain hepatic disorders. However, the role of psychophysical stress on NKT cell-dependent liver injury induced by alpha-GalCer still remains to be elucidated. In this study, we employed inescapable electric foot shock as the mode of psychophysical stress and evaluated its effect on alpha-GalCer-induced hepatitis. Pre-exposure of 12 hours of foot shock stress before alpha-GalCer administration significantly enhanced alpha-GalCer-triggered increase in serum alanine aminotransferase levels, followed by increases in both liver caspase-3 activity and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL)-positive hepatocytes, thus indicating that the liver NKT cell-dependent apoptotic response was exacerbated by stress. Foot shock stress also significantly increased both the number of liver NKT cells and Fas expression levels on hepatocytes. Pretreatment with RU-486, a glucocorticoid (GC) receptor antagonist, completely reversed such stress-induced enhancement of the alpha-GalCer-triggered serum alanine aminotransferase and hepatocyte Fas antigen responses. In contrast, such a reversal effect was not found in the mice pretreated with naloxone, a micro-opioid receptor antagonist, which thus suggests that an elevation of endogenous GCs, but not beta-endorphin, as responsible for such stress-induced aggravation in mouse hepatitis models. In conclusion, foot shock stress-induced elevation of endogenous GCs exacerbates alpha-GalCer-initiated hepatic apoptosis through the expansion of liver NKT cells and the up-regulation of hepatocyte Fas antigen.
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PMID:Electric foot shock stress-induced exacerbation of alpha-galactosylceramide-triggered apoptosis in mouse liver. 1505 17

Epithelial cells of the human endometrium and differentiated endometrial stromal cells express the corticotropin-releasing hormone (CRH) gene. CRH is also produced by human placental cytotrophoblast. Endometrial and placental CRH are under the endocrine control of gonadal steroids as well as under autocrine/paracrine regulation by prostanoids and interleukins. Human endometrium, myometrium and placenta express the relevant receptors. Human trophoblast and decidualized endometrial cells also express Fas ligand (FasL), a pro-apoptotic molecule. These findings suggest that intra-uterine CRH may participate in local inflammatory phenomena associated with blastocyst implantation, while FasL may assist with maternal immune tolerance to the semi-allograft embryo. A nonpeptidic CRH receptor type 1 (CRH-R1)-specific antagonist decreased the expression of FasL by human trophoblasts, suggesting that CRH regulates the pro-apoptotic potential of these cells in an auto-paracrine fashion. Invasive trophoblasts promoted apoptosis of activated Fas-expressing human T lymphocytes, an effect potentiated by CRH and inhibited by the CRH antagonist. Female rats treated with the CRH antagonist in the first 6 days of gestation had a dose-dependent decrease of endometrial implantation sites and live embryos as well as markedly diminished endometrial FasL expression. However, embryos of mothers lacking T cells (nude rats) and embryos of syngeneic matings were not rejected when mothers were treated with antalarmin, suggesting that the effect of antalarmin on embryonic implantation is not due to a nonspecific toxicity of this compound but a specific effect on T cells. Our data suggest important physiological roles of endometrial and placental CRH in the regulation of blastocyst implantation and early maternal tolerance.
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PMID:Endometrial and placental CRH as regulators of human embryo implantation. 1528 81

While corticotropin-releasing hormone (CRH) has been implicated in a variety of brain disorders such as ischemic injury, the molecular mechanism by which CRH elicits its activities is largely unclear. In the present study, we have determined the effect of CRH on oxygen-glucose deprivation (OGD) induced apoptosis in fetal hippocampal neurons. CRH alone at concentrations of 10-200 nM had no effect on neuronal apoptosis. However, when neurons were co-cultured with microglia, CRH alone at concentrations greater than 100 nM induced neuronal apoptosis and CRH potentiated significant neuronal apoptosis following exposure to OGD. The effect of CRH on neuronal apoptosis was inhibited in the presence of the CRH antagonist astressin. Real-time RT-PCR revealed an increase in mRNA levels of Fas ligand (Fas-L), a membrane protein related to the TNF family, in cultured microglia following OGD exposure. In the presence of CRH, OGD-induced Fas-L expression was significantly increased. The effect of CRH on Fas-L expression was inhibited by specific inhibitors of the extracellular signal-regulated protein kinase (PD98059) and p38 mitogen-activated protein kinase (SB203580). These results suggest that CRH potentiates neuronal apoptosis induced by OGD in the presence of microglia and that this effect may be mediated through the induction of proinflammatory mediators in microglia.
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PMID:Corticotropin-releasing hormone potentiates neural injury induced by oxygen-glucose deprivation: a possible involvement of microglia. 1551 43

Ultraviolet radiation is a well established epidemiologic risk factor for malignant melanoma. This observation has been linked to the relative resistance of normal melanocytes to ultraviolet B (UVB) radiation-induced apoptosis, which consequently leads to accumulation of UVB radiation-induced DNA lesions in melanocytes. Therefore, identification of physiologic factors regulating UVB radiation-induced apoptosis and DNA damage of melanocytes is of utmost biological importance. We show that the neuropeptide alpha-melanocyte-stimulating hormone (alpha-MSH) blocks UVB radiation-induced apoptosis of normal human melanocytes in vitro. The anti-apoptotic activity of alpha-MSH is not mediated by filtering or by induction of melanin synthesis in melanocytes. alpha-MSH neither leads to changes in the cell cycle distribution nor induces alterations in the expression of the apoptosis-related proteins Bcl(2), Bcl(x), Bax, p53, CD95 (Fas/APO-1), and CD95L (FasL). In contrast, alpha-MSH markedly reduces the formation of UVB radiation-induced DNA damage as demonstrated by reduced amounts of cyclobutane pyrimidine dimers, ultimately leading to reduced apoptosis. The reduction of UV radiation-induced DNA damage by alpha-MSH appears to be related to induction of nucleotide excision repair, because UV radiation-mediated apoptosis was not blocked by alpha-MSH in nucleotide excision repair-deficient fibroblasts. These data, for the first time, demonstrate regulation of UVB radiation-induced apoptosis of human melanocytes by a neuropeptide that is physiologically expressed within the epidermis. Apart from its ability to induce photoprotective melanin synthesis, alpha-MSH appears to exert the capacity to reduce UV radiation-induced DNA damage and, thus, may act as a potent protection factor against the harmful effects of UV radiation on the genomic stability of epidermal cells.
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PMID:alpha-Melanocyte-stimulating hormone protects from ultraviolet radiation-induced apoptosis and DNA damage. 1556 80


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