Prostaglandins

Bergström, Sune; Samuelsson, Bengt

doi:10.1146/annurev.bi.34.070165.000533

Cited by 99 publications

(19 citation statements)

References 11 publications

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“…Although they serve as important precursors for prostaglandin synthesis (Bergstrom, 1966), unsaturated fatty acids may also share equally crucial roles as receptor signals. For example, linoleic and arachidonic acids activate PPARa with a potency of 30 ,tM (Gottlicher et al, 1992;Banner et al, 1993;.…”

Section: Phytol Metabolites As Transcriptional Signalsmentioning

confidence: 99%

Phytol metabolites are circulating dietary factors that activate the nuclear receptor RXR.

Kitareewan

Burka

Tomer

et al. 1996

MBoC

179

135

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RXR is a nuclear receptor that plays a central role in cell signaling by pairing with a host of other receptors. Previously, 9-cis-retinoic acid (9cRA) was defined as a potent RXR activator. Here we describe a unique RXR effector identified from organic extracts of bovine serum by following RXR-dependent transcriptional activity. Structural analyses of material in active fractions pointed to the saturated diterpenoid phytanic acid, which induced RXR-dependent transcription at concentrations between 4 and 64 ,uM. Although 200 times more potent than phytanic acid, 9cRA was undetectable in equivalent amounts of extract and cannot be present at a concentration that could account for the activity. Phytenic acid, another phytol metabolite, was synthesized and stimulated RXR with a potency and efficacy similar to phytanic acid. These metabolites specifically displaced[3H]-9cRA from RXR with Ki values of 4 ,uM, indicating that their transcriptional effects are mediated by direct receptor interactions. Phytol metabolites are compelling candidates for physiological effectors, because their RXR binding affinities and activation potencies match their micromolar circulating concentrations. Given their exclusive dietary origin, these chlorophyll metabolites may represent essential nutrients that coordinate cellular metabolism through RXR-dependent signaling pathways.

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Section: Phytol Metabolites As Transcriptional Signalsmentioning

confidence: 99%

Phytol metabolites are circulating dietary factors that activate the nuclear receptor RXR.

Kitareewan

Burka

Tomer

et al. 1996

MBoC

179

135

View full text Add to dashboard Cite

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“…In any case, such a propensity to form the most unsaturated cholesteryl esters must explain their relative abundance in the adrenal cortex. Furthermore, the accumulation of these esters might be a means of storing arachidonic acid which is a precursor of the prostaglandins (29); the latter in turn might regulate the adrenal vasculature and blood perfusion; by their ACTH-like effects the prostaglandins might also exert a more direct control on steroid hormone production (30).…”

Section: Discussionmentioning

confidence: 99%

Metabolism of adrenal cholesterol in man

Borkowski¹,

Delcroix²,

Levin³

1972

J. Clin. Invest.

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A B S T R A C T The synthesis of adrenal cholesterol, its esterification and the synthesis of the glucocorticosteroid hormones were studied in vitro on human adrenal tissue.It was found that the synthesis of adrenal cholesterol may normally be small in the zona "fasciculata," particularly when compared with the synthesis of the glucocorticosteroid hormones, that it is several times higher in the zona "reticularis" where esterified cholesterol is less abundant, and that under ACTH stimulation it increases strikingly and proportionally to the degree of esterified adrenal cholesterol depletion.On the other hand, the relative rate of esterification as well as the concentration of free adrenal cholesterol are remarkably stable: they do not differ according to the adrenal zonation and are unaffected by ACTH. Furthermore, from a qualitative point of view, the relative proportions of A1 and A2 cholesteryl esters formed in situ are similar to those anticipated from their relative concentrations, suggesting that the characteristic fatty acid distribution of the adrenal cholesteryl esters results from an in situ esterification rather than from a selective uptake of the plasma cholesteryl esters. Besides, the in vitro esterification reveals a propensity to the formation of the most unsaturated cholesteryl esters.Regarding hydrocortisone and corticosterone, their synthesis tends to be more elevated in the zona "fasciculata." Despite its higher cholesterol concentration the zona "fasciculata" should not therefore be viewed as a

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“…Despite centuries of use, the action mechanism of acetylsalicylic acid (Aspirin) was not described until 1971 by Sir John Vane 1 who showed that acetylsalicylic acid was an inhibitor of prostaglandin synthesis (Vane, 1971). At this time, the prostaglandins 2 had already been structurally characterized by Sune Bergström and Bengt Samuelsson (Bergström, 1967;Bergström and Samuelsson, 1965;Samuelsson, 2012) making it possible to identify PGE as an inflammatory prostaglandin.…”

Section: Immune-to-brain Signalingmentioning

confidence: 99%

Talking to the Brain at the Blood-Brain Barrier through Inflammation-Induced Prostaglandin E2

Vasilache¹

2015

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The immune-to-brain signaling is a critical survival factor when the body is confronted by pathogens, and in particular by microorganisms. During infections, the ability of the immune system to engage the central nervous system (CNS) in the management of the inflammatory response is just as important as its ability to mount a specific immune response against the pathogen, since the CNS can provide a systemic negative feed-back to the immune activation by release of stress hormones and also can prioritize the usage of the energy resources by the vital organs. Prostaglandin E2 (PGE2) and pro-inflammatory cytokines were among the first mediators to be identified to participate in the immune-to-brain signaling, a process that is clinically recognized by the development of manifestations of common illness such as fever, anorexia, decreased social interactions, lethargy, sleepiness, and hyperalgesia.In this thesis the contribution of PGE2 to the immune-to-brain signaling was further characterized at the blood-brain-barrier (BBB) and in the anterior preoptic area (POA) of the hypothalamus (i.e. the thermoregulatory region or, in sickness, the fever generating region).BBB is the major interface region between peripheral circulating cytokines and the neuronal parenchyma and a critical source of PGE2. Using chimeric mice lacking the inducible enzyme for PGE2 synthesis, microsomal PGE synthase-1 (mPGES-1), in either hematopoietic or nonhematopoietic cells, we demonstrate in paper I that brain endothelial cells are the critical source of PGE2 in BBB during peripheral inflammation. For the demonstration of the mPGES-1 expression in the BBB cells we developed in paper I a method for enzymatic dissociation of these cells, followed by fluorescence activated cell sorting (FACS). Using the same method, we show in paper II that the BBB response to immune stimuli is towards an increased production of PGE2 in endothelial cells and an increased sensitivity of these cells for proinflammatory cytokines. These changes are supported by decreased PGE2 degradation and decreased synthesis of other prostanoids in perivascular macrophages, which hence respond in concordance with the endothelial cells in enhancing PGE2 signaling.Once released in the neuronal tissue, PGE2 has been shown to be critical for the fever response by acting on the type 3 PGE2 receptors (EP3) within POA. By laser capture microdissection (LCM) we extracted the EP3 receptor expressing region in POA, defined by in situ hybridization histochemistry, from mouse brain sections. We demonstrate in paper III that the predominant subtypes of the EP3 receptor in POA are EP3α and EP3γ. In paper IV we further analyze the effect of PGE2 on the LCM dissected EP-rich POA using gene expression microarrays. We demonstrate that PGE2 has a limited effect on the gene expression changes within POA, suggesting that the neuronal activity is modulated by PGE2 in a transcriptionindependent manner and that the profound gene expression changes that are seen in the CNS during inflammation ...

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Prostaglandins

Cited by 99 publications

References 11 publications

Phytol metabolites are circulating dietary factors that activate the nuclear receptor RXR.

Phytol metabolites are circulating dietary factors that activate the nuclear receptor RXR.

Metabolism of adrenal cholesterol in man

Talking to the Brain at the Blood-Brain Barrier through Inflammation-Induced Prostaglandin E2

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