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)

This paper discusses the current evidence supporting the notion that endogenous carbon monoxide (CO) is a modulator of neuroendocrine function. CO is normally formed in the body during the enzymatic catabolism of heme moieties by heme oxygenase (HO). Three HO isoforms have been described to date: HO-1, HO-2 and HO-3. In the brain, CO is principally generated by HO-2 but, in discrete brain areas such as the paraventricular nuclei of the hypothalamus, a role for HO-1 is also possible. Moreover, under pathological conditions, the latter isoform is expressed by activated glial cells. The possible contribution by the recently described HO-3 remains to be established. Once formed, CO exerts its biological effects mainly via the activation of soluble guanylyl cyclase, but alternative signaling mechanisms, such as the activation of cyclooxygenase or the inhibition of cytochrome P450, have also been reported. In in vitro studies, the formation of CO within the hypothalamus has been associated with inhibition of the release of hormones such as corticotropin-releasing hormone, arginine vasopressin and oxytocin involved in hypothalamo-pituitary-adrenal axis activation and, conversely, with stimulation of luteinising hormone-releasing hormone release, thus suggesting that the gas may have a neuroendocrine role which may be to prevent over-exuberant activation of the hypothalamo-pituitary-adrenal axis and inhibition of reproductive processes within the hypothalamus during stress. At present, however, the possible pathophysiological relevance of the in vitro observations remains to be demonstrated.
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PMID:The role of carbon monoxide in the regulation of neuroendocrine function. 965 Aug 14

Heme oxygenase (HO) catalyzes the first and rate-controlling step of heme catabolism into biliverdin, iron and carbon monoxide. Three isoforms of HO have been identified so far: the inducible HO-1 and the constitutive HO-2 and HO-3. Both HO-1 and HO-2 were expressed in zona fasciculata (ZF) adrenal cells and in a mouse adrenocortical cell line (Y1). HO-1 but not HO-2 expression was upregulated by adrenocorticotropic hormone (ACTH) and accumulation of HO-1 protein correlated with an increase in HO activity in Y1 cells. ACTH induced HO-1 expression in a time- and dose-dependent manner with a maximum after 5 h of treatment and a threshold concentration of 0.1 mIU/ml. Actinomycin D and cycloheximide completely blocked the effect of ACTH on HO-1 mRNA expression whereas mRNA stability was not affected by ACTH. Permeable analogs of cAMP mimicked the effect of ACTH on HO-1 expression and ACTH induction was prevented by the protein kinase A (PKA) inhibitor H89. Steroid production was significantly increased when both HO-1 and HO-2 activities were inhibited by Sn-protoporphyrin IX (SnPPIX). The lipid peroxidation and increase in carbonyl content triggered by hydrogen peroxide was prevented by treatment of Y1 cells with bilirubin and ACTH.
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PMID:Adrenocorticotropin induces heme oxygenase-1 expression in adrenal cells. 1470 50

Heme oxygenase (HO) cleaves the tetrapyrrolic ring of cellular heme moieties liberating carbon monoxide (CO) and equimolar amounts of free iron and biliverdin (BV). BV is in turn converted into bilirubin (BR) by the cytosolic enzyme BV reductase. Three HO isoforms have been described to date: HO-1, HO-2, and HO-3. All these isoforms are present in nervous tissue with different localizations and regulation. CO, the gaseous product of HO, exerts its biological effects through the activation of soluble guanylyl cyclase, but alternative signaling pathways, such as the activation of cyclooxygenase, have also been reported in the brain. In vitro and in vivo studies showed that CO, at the hypothalamic level, plays a key role in the modulation of stress response because it inhibits the release of antiinflammatory neuropeptides, such as corticotropin-releasing hormone and arginine vasopressin, and increases body temperature in rodents exposed to psychological stressors (stress fever). In the last few years, a new role of BR as an endogenously produced antioxidant has emerged, and several reports have shown that BR contributes to prevent cell damage mediated by reactive oxygen species, as well as nitric oxide and its congeners.
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PMID:Heme oxygenase and its products in the nervous system. 1534 48