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)

Opioid peptides, particularly beta-endorphin, methionine- (MEK) and leucine-enkephalin, and dynorphin, are involved in the regulation of food intake in mammals. The precursor molecules of these peptides undergo differential processing in brain areas producing regional concentration differences in opioids. Intraregional concentration changes also accompany alterations in feeding states. For example, MEK concentrations decrease in the basomedial hypothalamus, amygdala, and olfactory bulb in fed sheep compared with fasted sheep. Moreover, these changes are species specific. In sheep, beta-endorphin decreases in the dorsomedial and posterior hypothalami after feeding, but in the rat it is increased in the ventromedial hypothalamus and decreased in the posterior hypothalamus. In addition, immunohistochemical localization of cell bodies shows interspecies differences in concentrations. For example, dynorphin is found predominantly in the suprachiasmatic area in sheep, but in the paraventricular nucleus in the rat. These observations indicate that regulation of food intake may be differentially controlled in these species. In sheep, kappa agonists increase food intake, whereas stimulation of delta receptors inhibits feeding. Further clarification of the receptors involved in food intake will necessitate studies with more specific agonists.
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PMID:Opioid peptides and the control of feeding in sheep. 302 55

The antinociceptive effect of intracerebroventricular injection (icv) of Asn-Ala-Gly-Ala (NAGA), a partial sequence of beta-lipotropin, was studied in rats. The potassium iontophoresis-induced tail flick was used to measure the pain threshold. The antinociceptive effect of NAGA, which was dose-dependent (icv, 0.03-0.24 mumol/rat) and long-lasting (90 min), was reversed by naloxone (icv, 0.26 mg.kg-1) and inhibited by anti-MEK serum (titre: 1:5000, 5 microliters) or anti-LEK serum (titre: 1:5000, 5 microliters). NAGA-induced antinociception was scarcely affected by anti-beta-EP serum (titre: 1:30,000, 5 microliters) or anti-Dyn A1-13 serum (titre: 1:30,000, 5 microliters). It was suggested that the antinociceptive effect of NAGA may be associated with the release of met-enkephalin and leu-enkephalin in rat brain.
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PMID:Antinociceptive effect of intracerebroventricular injection of a tetrapeptide Asn-Ala-Gly-Ala in rats. 770 46

We have previously demonstrated that corticotropin-releasing hormone (CRH) receptor 1 (CRH-R1) is functionally expressed in rat microglia. In the present study, we show that CRH, acting on CRH-R1, promoted cell proliferation and tumour necrosis factor-alpha (TNF-alpha) release in cultured rat microglia. Exogenous CRH resulted in an increase in BrdU incorporation compared with control cells, which was observed in a range of concentrations of CRH between 10 and 500 nm, with a maximal response at 50 nm. The effect of CRH on BrdU incorporation was inhibited by a CRH antagonist astressin but not by a cAMP-dependent protein kinase inhibitor H89. Exposure of microglial cells to CRH resulted in a transient and rapid increase in TNF-alpha release in a dose-dependent manner. In the presence of astressin, the effects of CRH on TNF-alpha release were attenuated. CRH effects on TNF-alpha release were also inhibited by specific inhibitors of MEK, the upstream kinase of the extracellular signal-regulated protein kinase (ERK) (PD98059) or p38 mitogen-activated protein kinase (SB203580), but not by H89. Furthermore, CRH induced rapid phosphorylation of ERK and p38 kinases. Astressin, PD98059, and SB230580 were able to inhibit CRH-induced kinase phosphorylation. These results suggest that CRH induces cell proliferation and TNF-alpha release in cultured microglia via MAP kinase signalling pathways, thereby providing insight into the interactions between CRH and inflammatory mediators.
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PMID:Corticotropin-releasing hormone induces proliferation and TNF-alpha release in cultured rat microglia via MAP kinase signalling pathways. 1248 15

Regulation of intracellular transport plays a role in a number of processes, including mitosis, determination of cell polarity, and neuronal growth. In Xenopus melanophores, transport of melanosomes toward the cell center is triggered by melatonin, whereas their dispersion throughout the cytoplasm is triggered by melanocyte-stimulating hormone (MSH), with both of these processes mediated by cAMP-dependent protein kinase A (PKA) activity [1, 2]. Recently, the ERK (extracellular signal-regulated kinase) pathway has been implicated in regulating organelle transport and signaling downstream of melatonin receptor [3, 4]. Here, we directly demonstrate that melanosome transport is regulated by ERK signaling. Inhibition of ERK signaling by the MEK (MAPK/ERK kinase) inhibitor U0126 blocks bidirectional melanosome transport along microtubules, and stimulation of ERK by constitutively active MEK1/2 stimulates transport. These effects are specific because perturbation of ERK signaling has no effect on the movement of lysosomes, organelles related to melanosomes [5]. Biochemical analysis demonstrates that MEK and ERK are present on melanosomes and transiently activated by melatonin. Furthermore, this activation correlates with an increase in melanosome transport. Finally, direct inhibition of PKA transiently activates ERK, demonstrating that ERK acts downstream of PKA. We propose that signaling of organelle bound ERK is a key pathway that regulates bidirectional, microtubule-based melanosome transport.
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PMID:Regulation of bidirectional melanosome transport by organelle bound MAP kinase. 1575 41

Paraventricular hypothalamic (PVH) corticotropin-releasing hormone (CRH) neuroendocrine neurons mount neurosecretory and transcriptional responses to glycemic challenges [intravenous 2-deoxyglucose (2-DG) or insulin]. Although these responses require signals from intact afferents originating from hindbrain CA (catecholaminergic) neurons, the identity of these signals and the mechanisms by which they are transduced by PVH neurons during glycemic challenge remain unclear. Here, we tested whether the prototypical catecholamine, norepinephrine (NE), can reproduce PVH neuroendocrine responses to glycemic challenge. Because these responses include phosphorylation of p44/42 mitogen-activated protein (MAP) kinases [extracellular signal-regulated kinases 1/2 (ERK1/2)], we also determined whether NE activates ERK1/2 in PVH neurons and, if so, by what mechanism. We show that systemic insulin and 2-DG, and PVH-targeted NE microinjections, rapidly elevated PVH phospho-ERK1/2 levels. NE increased Crh and c-fos expression, together with circulating ACTH/corticosterone. However, because injections also increased c-Fos mRNA in other brain regions, we used hypothalamic slices maintained in vitro to clarify whether NE activates PVH neurons without contribution of inputs from distal regions. In slices, bath-applied NE triggered robust phospho-ERK1/2 immunoreactivity in PVH (including CRH) neurons, which attenuated markedly in the presence of the alpha1 adrenoceptor antagonist, prazosin, or the MAP kinase kinase (MEK) inhibitor, U0126 (1,4-diamino-2,3-dicyano-1,4-bis[2-aminophenylthio]butadiene). Therefore, at a systems level, local PVH delivery of NE is sufficient to account for hindbrain activation of CRH neuroendocrine neurons during glycemic challenge. At a cellular level, these data provide the first demonstration that MAP kinase signaling cascades (MEK-->ERK) are intracellular transducers of noradrenergic signals in CRH neurons, and implicate this transduction mechanism as an important component of central neuroendocrine responses during glycemic challenge.
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PMID:Catecholaminergic control of mitogen-activated protein kinase signaling in paraventricular neuroendocrine neurons in vivo and in vitro: a proposed role during glycemic challenges. 1761 Dec 87

Corticotropin releasing factor (CRF) mediates various responses to stress through CRF receptors 1 and 2. CRF receptor 2 has two forms, 2alpha and 2beta each of which appears to have distinct roles. Here we used dopaminergic neuron-derived MN9D cells to investigate the function of CRF receptor 2 in dopamine neurons. We found that n-butyrate, a histone deacetylase inhibitor, induced MN9D cell differentiation and increased gene expression of all CRF receptors. CRF receptor 2beta was minimally expressed in MN9D cells; however, its expression dramatically increased during differentiation. CRF receptor 2beta expression levels appeared to correlate with neurite outgrowth, suggesting CRF receptor 2beta involvement in neuronal differentiation. To validate this statement, we made a CRF receptor 2beta-overexpressing MN9D/CRFR2 beta stable cell line. This cell line showed robust neurite outgrowth and GAP43 overexpression, together with MEK and ERK activation, suggesting MN9D cell neuronal differentiation. From these results, we conclude that CRF receptor 2beta plays an important role in MN9D cell differentiation by activating the MEK/ERK signaling pathway.
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PMID:Involvement of corticotropin-releasing factor receptor 2 beta in differentiation of dopaminergic MN9D cells. 1851 79

Cimicifuga rhizoma has long been used in traditional Korean medicine. In particular, a Cimicifuga heracleifolia extract (CHE) was reported to inhibit the formation of glutamate and the glutamate dehydrogenase activity in cultured rat islet. Glutamate activates melanogenesis by activating tyrosinase. Accordingly, it was hypothesized that a CHE might inhibit the melanogenesis-related signal pathways including the inhibition of microphthalmia-associated transcription factor (MITF)-tyrosinase signaling and/or the activation of extracellular signal-regulated kinase (ERK)-Akt signaling. The results showed that CHE inhibits the cellular melanin contents, tyrosinase activity and expression of melanogenesis-related proteins including MITF, tyrosinase and tyrosinase-related protein (TRP)s in alpha-melanocyte-stimulating hormone-stimulated B16 cells. Moreover, CHE phosphorylates MEK, ERK1/2 and Akt, which are melanogenesis inhibitory proteins. The data suggest that CHE inhibits melanogenesis signaling by both inhibiting the tyrosinase directly and activating the MEK-ERK or Akt signal pathways-mediated suppression of MITF and its downstream signal pathway, including tyrosinase and TRPs. Therefore, C. heracleifolia would be a useful therapeutic agent for treating hyperpigmentation and an effective component in whitening and/or lightening cosmetics.
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PMID:Dichloromethane fraction of Cimicifuga heracleifolia decreases the level of melanin synthesis by activating the ERK or AKT signaling pathway in B16F10 cells. 1880 55

Prolactin (PRL), the major lactogenic hormone, acts also as neuromodulator and regulator of neuronal and glial plasticity in the brain. There is an increase in synthesis and release of PRL within the hypothalamus during peripartum and in response to stress. To identify mechanisms by which PRL induces neuroplasticity, we studied the ability of PRL to induce the transcription factor Egr-1 in the hypothalamic cell line, 4B, in vitro, and in specific neuronal cell types of the hypothalamus in vivo. PRL induced Egr-1 mRNA expression in 4B cells, an effect which was prevented by the MEK inhibitor, U0126. In vivo, intracerebroventricular PRL (1 microg) increased Egr-1 mRNA levels in the hypothalamic paraventricular (PVN) and supraoptic nuclei (SON) of female rats. The increase in mRNA paralleled elevated Egr-1 protein expression in the PVN and SON. Double staining immunohistochemistry revealed Egr-1 localization in oxytocin neurons of the PVN and SON, but not in vasopressin neurons in these regions. In the dorsomedial PVN, a population of non-oxytocin or vasopressin cells localized in a region corresponding to corticotropin-releasing hormone neurons also showed marked Egr-1 immunoreactivity. The data suggest that PRL modulates plasticity in oxytocinergic neurons, through MAP kinase-dependent induction of Egr-1.
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PMID:Prolactin induces Egr-1 gene expression in cultured hypothalamic cells and in the rat hypothalamus. 1976 48

Corticotropin releasing factor (CRF) is considered as the central driving force in the stress response and plays a key role in the pathogenesis of depression. CRF neurons have been identified to locate in most regions of the prefrontal cortex (PFC), a brain region that is highly associated with the control of emotion and cognition. However, little is known on the regulation of CRF in this region. In this study, we aimed to identify the regulatory effect of acute restraint stress and glucocorticoid on PFC CRF and characterize the possible function of CRF in the PFC. We found that acute restraint stress increased and glucocorticoid decreased PFC CRF mRNA expression. The expression of glucocorticoid receptor (GR) was found to colocalize with CRF neurons in the PFC. In addition, recruitment of GR by the CRF promoter was observed in vivo. Specific attention was paid to the effect of CRF on CRF receptor 1 (CRFR1) expression in primary PFC cultures. The results showed that CRF increased CRFR1 expression through the MEK-ERK1/2 pathway. In summary, this study may contribute to the better understanding of CRF functions in the PFC.
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PMID:Stress and glucocorticoids regulated corticotropin releasing factor in rat prefrontal cortex. 2166 19

Melanin plays major a role in pigmentation of hair, eyes, and skin in mammals. In this study, the inhibitory effects of MMS 1001 on alpha-MSH-stimulated melanogenesis were investigated in B16F10 melanoma cells. MMS 1001 did not show cytotoxic effects up to 10 microM. Melanin content and intracellular tyrosinase activity were inhibited by MMS 1001 treatment in a dose-dependent manner. In Western blot analysis, MITF expression was decreased by MMS 1001. In addition, tyrosinase expressions were also reduced after MMS 1001 treatment. Further results showed that the phosphorylation of ERK was induced by MMS 1001. Moreover, a specific MEK inhibitor, PD98059, abrogated the inhibitory effects of MMS 1001 on melanin production and tyrosinase expression. These results indicate that the hypopigmentary effects of MMS 1001 resulted from the inhibition of MITF and tyrosinase expression via phosphorylation of ERK. Thus, MMS 1001 could be developed as a new effective skin-whitening agent.
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PMID:MMS 1001 inhibits melanin synthesis via ERK activation. 2355 41


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