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)

Ultraviolet B (UVB) radiation is known to induce reactive oxygen species (ROS) in the skin. The skin, however, counteracts ROS by both constitutional and newly produced antioxidants. One such antioxidant, adult T cell leukemia-derived factor (ADF), a human homologue of thioredoxin (TRX), was shown to be efficiently produced in and released from cultured normal human keratinocytes after UVB irradiation by Northern and Western blot analyses and enzyme-linked immunoabsorbent assay (ELISA). Recombinant ADF (rADF) did not rescue UVB-induced melanocyte death, either when added pre- or post-UV irradiation. However, further addition of neutralizing antibody caused cell death of both keratinocytes and melanocytes. rADF was shown to induce higher expression in melanocortin-1 receptor (MC1-R) mRNA accompanied by increased binding activity using 125I labeled [Nle4, D-Phe7]-alpha-MSH in melanocytes, leading to the enhanced increment of DNA synthesis. Taken together, it was shown that released ADF from UVB-irradiated keratinocytes acts as a survival factor for both keratinocytes and melanocytes but does not rescue UV-induced melanocyte death. Further, it may work as one of the stimulatory factors for UVB-induced melanogenesis by upregulating MSH-R binding activity in combination with the enhanced DNA synthesis by alpha-MSH.
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PMID:The effect of ultraviolet B induced adult T cell leukemia-derived factor/thioredoxin (ADF/TRX) on survival and growth of human melanocytes. 917 Jan 66

An important constituent of the cellular antioxidant buffering system that controls the redox state of proteins is thioredoxin (TRX), a 13 kDa protein that catalyzes thiol-disulfide exchange reactions, regulates activation of transcription factors, and possesses several other biologic functions similar to cytokines. We have previously reported that TRX released from UVB-irradiated keratinocytes stimulates melanogenesis by upregulating MSH receptor expression and its binding activity in melanocytes. The purpose of this study was to examine the effects of TRX on keratinocytes as an autocrine factor. TRX suppressed the UVB-induced production and secretion of alpha-melanocyte stimulating hormone (alpha-MSH) and of adrenocorticotropic hormone (ACTH), and also suppressed proopiomelanocortin (POMC) mRNA expression by normal human keratinocytes; however, TRX upregulated melanocortin 1 receptor (MC1-R) expression synergistically with UVB in normal human keratinocytes. These results suggest that exogenous TRX regulates expression of those genes in different manners. Furthermore, addition of an antibody against TRX induced cell death in keratinocytes, probably due to enhanced signaling of MSH, as it has been shown that MSH suppresses heat shock protein (hsp) 70 expression in differentiated keratinocytes, which express high levels of MC1-R and decreases their survival rate during oxidative stress. Taken together, the results suggest that keratinocyte-derived TRX regulates the expression of stress inducible neuropeptides and their receptor, and is critically involved in the survival of keratinocytes.
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PMID:The effect of thioredoxin on the expression of proopiomelanocortin-derived peptides, the melanocortin 1 receptor and cell survival of normal human keratinocytes. 1176 82

The hypothalamic-pituitary-adrenal (HPA) axis is critical to mediating the body's response to stress. Corticotropin releasing hormone (CRH) plays a central role in controlling the stress response and regulating the HPA axis. Recent findings support CRH participates in the stress-induced hippocampal neuron apoptosis, but the underlying mechanisms are not fully understood. Our present study demonstrates that CRH can independently decrease hippocampal neuron cell viability in vitro in a concentration- and time-dependent manner. CRH receptor 1 (CRHR1) is involved in CRH-induced neuron apoptosis. Endoplasmic reticulum (ER) stress response marker, glucose-regulated protein 78 (GRP78), either protein or mRNA, is significantly elevated after treatment of CRH, and decreased when co-treated with salubrinal, ER stress inhibitor. The ER stress associated proapoptotic transcription factor C/EBP homologous protein (CHOP) and cleavage of caspase-12 protein expression are also increased following CRH treatment. Furthermore, we investigate which ER stress cascades are affected by CRH. CRH activates inositol-requiring enzyme 1 (IRE1), apoptosis signal regulating kinase 1 (ASK1), and c-jun kinase (JNK). Neuron apoptotic rate, examined by flow cytometry, is increased when CRH treatment and attenuated by salubrinal, thioredoxin (ASK1 inhibitor) and SP600125 (JNK inhibitor). Therefore, current data indicate that ER stress, through activating the IRE1/ASK1/JNK cascade, plays an important role in CRH-induced neuron apoptosis.
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PMID:Endoplasmic reticulum stress contributes to CRH-induced hippocampal neuron apoptosis. 2228 33

Selenoprotein T (SELENOT, SELT) is a thioredoxin-like enzyme anchored at the endoplasmic reticulum (ER) membrane, whose primary structure is highly conserved during evolution. SELENOT is abundant in embryonic tissues and its activity is essential during development since its gene knockout in mice is lethal early during embryogenesis. Although its expression is repressed in most adult tissues, SELENOT remains particularly abundant in endocrine organs such as the pituitary, pancreas, thyroid and testis, suggesting an important role of this selenoprotein in hormone production. Our recent studies showed indeed that SELENOT plays a key function in insulin and corticotropin biosynthesis and release by regulating ER proteostasis. Although SELENOT expression is low or undetectable in most cerebral structures, its gene conditional knockout in brain provokes anatomical alterations that impact mice behavior. This suggests that SELENOT also plays an important role in brain development and function. In addition, SELENOT is induced after injury in brain or liver and exerts a cytoprotective effect. Thus, the data gathered during the last ten years of intense investigation of this newly discovered thioredoxin-like enzyme point to an essential function during development and in adult endocrine organs or lesioned brain, most likely by regulating ER redox circuits that control homeostasis and survival of cells with intense metabolic activity.
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PMID:Selenoprotein T is a key player in ER proteostasis, endocrine homeostasis and neuroprotection. 2980 Jun 53