Dexamethasone-Induced Change in the Sphingomyelin Content of Human Polymorphonuclear Leukocytes in Vitro*

Nelson, Don H.; Murray, Darrell K.; Brady, Roscoe O.

doi:10.1210/jcem-54-2-292

Cited by 33 publications

(9 citation statements)

References 24 publications

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“…there was a 50% increase in the sphingomyelin in the plasma membrane-enriched fraction but no significant change in sphingomyelin in the whole cells. The concentration ofdexamethasone employed in these studies is comparable to that which was shown previously to increase the sphingomyelin content of human polymorphonuclear leukocytes and ghosts of rat epididymal fat cells (3,5).…”

Section: Discussionsupporting

confidence: 73%

“…The cells scraped from the dishes were disrupted by sonication and the activity of the phosphatidylcholine:ceramidecholinephosphotransferase pathway was determined by measuring the amount of 14C-labeled sphingomyelin produced by incubation with phosphatidyl[methyl-' Clcholine (5). The results of these studies presented in Fig.…”

Section: Resultsmentioning

confidence: 99%

“…We have previously demonstrated an effect of dexamethasone and adrenalectomy upon the sphingomyelin content of human leukocytes and ghosts of rat epididymal fat cells (3)(4)(5).…”

mentioning

confidence: 99%

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Dexamethasone increases the synthesis of sphingomyelin in 3T3-L1 cell membranes.

Nelson¹,

Murray²

1982

Proc. Natl. Acad. Sci. U.S.A.

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An acute increase in the sphingomyelin content of a plasma membrane-enriched fraction of 3T3-LI cells was produced by incubation of the cells with 0.1 FLM dexamethasone for 4 hr. Dexamethasone also stimulated the activity of the pathway of sphingomyelin synthesis by utilizing the phosphorylcholine of phosphatidylcholine as a donor to ceramide to synthesize the phospholipid (phosphatidylcholine:ceramide cholinephosphotransferase). Dexamethasone-stimulated increase in the utilization of 14C-labeled choline of phosphatidylcholine for the synthesis of sphingomyelin was inhibited by the addition of cycloheximide to the incubation. Therefore, it appears that corticosteroid stimulation of new protein synthesis was required to produce the effect. An increase in the enzymatic pathway by 83% and of the sphingomyelin content of the plasma membrane-enriched fraction by 50% after incubation with dexamethasone for 4 hr demonstrates the rapidity with which the hormone can produce considerable remodeling of the membrane. The increase in the synthetic pathway in the plasma membrane-enriched fraction was sufficient to account for the measured increase in sphingomyelin. It appears likely that the large increase in membrane sphingomyelin could contribute significantly to the many demonstrated effects of corticosteroids upon membrane processes, including transport, receptors, and enzymatic activity.Corticosteroids have widespread effects on the function ofmost cells (1, 2). In the whole animal, deficiency or chronic excess is incompatible with survival. Glucocorticoids are essential for the growth of many cells in culture and have effects upon receptors, enzyme activity, and membrane transport. Most of these effects are thought to be secondary to steroid-receptor interactions influencing protein synthesis, but the proteins or enzymes involved have been identified in only a few instances.We have previously demonstrated an effect of dexamethasone and adrenalectomy upon the sphingomyelin content of human leukocytes and ghosts of rat epididymal fat cells (3-5).These effects have been seen both in vitro and in vivo, and cells obtained from adrenalectomized and intact animals have responded to the hormones. Fat cell ghosts from the adrenalectomized animals contain less sphingomyelin than those obtained from intact animals and undergo a greater increase when exposed to the corticosteroid. Studies of this action of corticosteroids and the mechanism by which it is produced were undertaken with 3T3-L1 cells in culture. METHODS3T3-L1 fibroblasts, obtained from the American Type Culture Collection (Rockville, MD), were cultured in Dulbecco's modified Eagle's medium with 10% fetal calf serum in the presence of 5% CO2 in air. After cells became confluent, they were incubated in media and 10% calf serum at 370C with and without 0.1 AM dexamethasone for 4 hr. When cycloheximide was added to the incubations it was at a concentration of 2 jig/ml.At the end of the incubation period, cells (=7 X 106) were washed with Hanks' balanced salt solut...

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Section: Discussionsupporting

confidence: 73%

Section: Resultsmentioning

confidence: 99%

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Dexamethasone increases the synthesis of sphingomyelin in 3T3-L1 cell membranes.

Nelson¹,

Murray²

1982

Proc. Natl. Acad. Sci. U.S.A.

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“…Notably, the glucocorticoid increased membrane sphingomyelin in rat epididymal fat cells (41). Dexamethasone was subsequently shown to increase sphingomyelin levels in HeLa cells (42) and human polymorphonuclear leukocytes (17), ceramide levels in a murine B lymphoma cell line (16), and sphingosine levels in 3T3-L1 preadipocytes (43). In vivo, epididymal fat cell ghosts isolated from adrenalectomized rats demonstrated decreased sphingomyelin levels, which could be restored by the administration of dexamethasone (44).…”

mentioning

confidence: 98%

“…Dexamethasone increases the expression and/or activity of SPT (45) and neutral and acidic forms of sphingomyelinase (17,43,46,47). These observations are consistent with the established roles of glucocorticoid receptors as transcription factors whose entry into the nucleus is regulated by ligand binding.…”

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confidence: 99%

A Role for Sphingolipids in Producing the Common Features of Type 2 Diabetes, Metabolic Syndrome X, and Cushing’s Syndrome

2005

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Metabolic syndrome X and type 2 diabetes share many metabolic and morphological similarities with Cushing's syndrome, a rare disorder caused by systemic glucocorticoid excess. Pathologies frequently associated with these diseases include insulin resistance, atherosclerosis, susceptibility to infection, poor wound healing, and hypertension. The similarity of the clinical profiles associated with these disorders suggests the influence of a common molecular mechanism for disease onset. Interestingly, numerous studies identify ceramides and other sphingolipids as potential contributors to these sequelae. Herein we review studies demonstrating that aberrant ceramide accumulation contributes to the development of the deleterious clinical manifestations associated with these diseases. Diabetes 54:591-602, 2005

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Female hormones reduce neutrophil responsiveness in vitro

Buyon

Korchak

Rutherford

et al. 1984

Arthritis & Rheumatism

101

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Neutrophils were preincubated with 17 betaestradiol and progesterone to determine the effects of these hormones on chemotactic peptidestimulated superoxide anion (02-) generation and degranulation. At pharmacologic levels 17 beta-estradiol was more active than progesterone with respect to inhibition of 02-generation as well as degranulation. An increase of preincubation time from 5 minutes to 25 minutes increased the percent inhibition. When 17 beta+stradiol and progesterone were combined at levels which approximate those measured during gestation, there was small but significant inhibition of 02-generation. Dexamethasone at equal molar concentration inhibited 02-generation only after 25 minutes of preincubation and at no time reached the level of inhibition attained by either of the sex hormones alone. Both estradiol and progesterone at pharmacologic levels significantly inhibited betaglucuronidase and lysozyme release, whereas dexamethasone did not inhibit degranulation despite prolonged preincubation. Neutrophils isolated from women during various phases of the menstrual cycle and during the -

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Dexamethasone-Induced Change in the Sphingomyelin Content of Human Polymorphonuclear Leukocytes in Vitro*

Cited by 33 publications

References 24 publications

Dexamethasone increases the synthesis of sphingomyelin in 3T3-L1 cell membranes.

Dexamethasone increases the synthesis of sphingomyelin in 3T3-L1 cell membranes.

A Role for Sphingolipids in Producing the Common Features of Type 2 Diabetes, Metabolic Syndrome X, and Cushing’s Syndrome

Female hormones reduce neutrophil responsiveness in vitro

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