The Effects of Glucocorticoids on the Distribution and Mobilisation of Arachidonic Acid in Fat Cell Ghosts

Lewis, George; Piper, Priscilla J.; Vigo, Carmen

doi:10.1111/j.1476-5381.1979.tb08693.x

Cited by 14 publications

(3 citation statements)

References 34 publications

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“…There is evidence of a steady state turnover of free arachidonic acid in I 2 3 4 S 6 3 3 3 2 2 2 normal human skin (Black et al, 1978). Our findings suggest that in healthy skin this fatty acid may be continuously synthesised from steroid insensitive sources including triglycerides (Lewis et al, 1979), and cholesterol (Vahouny et al, 1978). The lack of effect of prednisolone on urinary PGF-M in vivo also suggests that this metabolite is derived from arachidonic acid, which originates from sources other than the steroid-sensitive phospholipase A2 pathway.…”

Section: Discussionmentioning

confidence: 61%

The effect of systemic prednisolone on arachidonic acid, and prostaglandin E2 and F2 alpha levels in human cutaneous inflammation.

Black¹,

Greaves²,

Hensby³

1982

Brit J Clinical Pharma

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1 In order to test the proposal that the anti-inflammatory effect of corticosteroids is attributable to inhibition of release of the prostaglandin precursor, arachidonic acid, the effect of systemic prednisolone on arachidonic acid and prostaglandin levels in abdominal skin of six patients receiving this treatment for alopecia totalis, was studied. 2 Inflammation was produced in an area of abdominal skin by topical application of 5% w/w tetrahydrofurfuryl nicotinate (THFN) cream. 3 The erythema produced was assessed visually, and exudate recovered from normal and inflamed skin, by a suction bulla technique. 4 Arachidonic acid and PGE2 and PGF2 alpha levels, as measured by gas chromatograph-mass spectrometry (GC-MS) were significantly elevated in the reddened (THFN) treated skin, compared with control areas. 5 After prednisolone treatment both arachidonic acid and prostaglandin levels in THFN-treated areas were suppressed near to values obtained from untreated skin, before prednisolone therapy. There was partial reduction of THFN induced erythema in three out of six subjects. Levels of arachidonic acid on control skin were not affected by the steroid. 6 These results provide direct evidence that steroids inhibit prostaglandin formation by blocking evoked rise in the concentration of free arachidonic acid. The relationship of this effect, in human skin, to the anti-inflammatory action of systemic steroids is uncertain.

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Section: Discussionmentioning

confidence: 61%

The effect of systemic prednisolone on arachidonic acid, and prostaglandin E2 and F2 alpha levels in human cutaneous inflammation.

Black¹,

Greaves²,

Hensby³

1982

Brit J Clinical Pharma

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“…Arachidonic acid mobilization, along with the formation of prostaglandin E2 and prostaglandin 12, has been reported in white adipocytes in response to noradrenaline, angiotensin, vasopressin and bradykinin (Dalton & Hope, 1974; Axelrod & Levine, 1981;Axelrod et al, 1985), but the contribution of phospholipids as the large triacylglycerol store, which can incorporate and liberate radiolabelled arachidonic acid. This problem was obviated by Lewis et al (1979), who demonstrated mobilization of arachidonic acid in fat-cell ghosts, which are devoid of most of their triacylglycerol. In this system, release of arachidonic acid could be accounted for by the hydrolysis of membrane phospholipids.…”

Section: Introductionmentioning

confidence: 99%

The α1-adrenergic transduction system in hamster brown adipocytes. Release of arachidonic acid accompanies activation of phospholipase C

Schimmel

1988

Biochemical Journal

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Previous studies of brown adipocytes identified an increased breakdown of phosphoinositides after selective alpha 1-adrenergic-receptor activation. The present paper reports that this response, elicited with phenylephrine in the presence of propranolol and measured as the accumulation of [3H]inositol phosphates, is accompanied by increased release of [3H]arachidonic acid from cells prelabelled with [3H]arachidonic acid. Differences between stimulated arachidonic acid release and formation of inositol phosphates included a requirement for extracellular Ca2+ for stimulated release of arachidonic acid but not for the formation of inositol phosphates and the preferential inhibition of inositol phosphate formation by phorbol 12-myristate 13-acetate. The release of arachidonic acid in response to phenylephrine was associated with an accumulation of [3H]arachidonic acid-labelled diacylglycerol, and this response was not dependent on extracellular Ca2+ but was partially prevented by treatment with the phorbol ester. The release of arachidonic acid was also stimulated by melittin, which increases the activity of phospholipase A2, by ionophore A23187, by lipolytic stimulation with forskolin and by exogenous phospholipase C. The arachidonic acid response to phospholipase C was completely blocked by RHC 80267, an inhibitor of diacylglycerol lipase, but this inhibitor had no effect on release stimulated with melittin or A23187 and inhibited phenylephrine-stimulated release by only 40%. The arachidonate response to forskolin was additive with the responses to either phenylephrine or exogenous phospholipase C. These data indicate that brown adipocytes are capable of releasing arachidonic acid from neutral lipids via triacylglycerol lipolysis, and from phospholipids via phospholipase A2 or by the sequential activities of phospholipase C and diacylglycerol lipase. Our findings also suggest that the action of phenylephrine to promote the liberation of arachidonic acid utilizes both of these reactions.

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“…Glucocorticoids mediate their effects by influencing gene expression and protein synthesis at essentially all known levels of regulation. Due to their lipophilicity, glucocorticoids may also modify membrane fluidity [15]. The various known effects of glucocorticoids (gene regulation, alteration of membrane fluidity, reduction of inflammation and immunity) may thus represent a successful way to improve gene transfer to cells ex vivo and in vivo.…”

Section: Introductionmentioning

confidence: 99%

In vitro and in vivo effects of glucocorticoids on gene transfer to skeletalmuscle

1999

FEBS Letters

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As a pharmacological approach to potentially improve gene transfer efficiency into skeletal muscle cells, glucocorticoids were shown here to allow efficient transfection of cultured and mouse human myoblasts, human pulmonary A549 cells, but not dog myoblasts, independently of the transfection protocol, the reporter gene and the transcription promoter employed. Transduction with adenovirus was also increased by dexamethasone. Pretreatment of cells 48 h prior to transfection was most effective and was shown to be concentration-dependent. This effect is mediated by binding to the glucocorticoid receptor, but not by glucocorticoid responsive elements present in the vectors. The acute dexamethasone effect could be due to increased plasmid entry into the cells as suggested by Southern blot, whereas the sustained increase of luciferase activity in dexamethasone-treated cultures may be related to intracellular mechanisms following cell entry. In mice in vivo, a similar increase of luciferase activity upon glucocorticoid treatment was found.

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The Effects of Glucocorticoids on the Distribution and Mobilisation of Arachidonic Acid in Fat Cell Ghosts

Cited by 14 publications

References 34 publications

The effect of systemic prednisolone on arachidonic acid, and prostaglandin E2 and F2 alpha levels in human cutaneous inflammation.

The effect of systemic prednisolone on arachidonic acid, and prostaglandin E2 and F2 alpha levels in human cutaneous inflammation.

The α1-adrenergic transduction system in hamster brown adipocytes. Release of arachidonic acid accompanies activation of phospholipase C

In vitro and in vivo effects of glucocorticoids on gene transfer to skeletalmuscle

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