Inhibitors of phospholipase A2 block the stimulation of protein synthesis by insulin in L6 myoblasts

Southorn, B G; Palmer, Robert M.

doi:10.1042/bj2700737

Cited by 24 publications

(10 citation statements)

References 14 publications

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“…Dexamethasone induces glutamine synthetase in L6 myoblasts, with a significant decrease of total protein synthesis (Max et al, 1987). Moreover, its interference with growth factor circuits has been documented in different normal myogenic models (Whitson et al, 1989;Southorn & Palmer, 1990;Poon et al, 1991).…”

Section: Resultsmentioning

confidence: 99%

Uncoupling of growth inhibition and differentiation in dexamethasone-treated human rhabdomyosarcoma cells

Giovanni

Lollini²,

Dolcetti³

et al. 1993

Br J Cancer

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Summary The effects of dexamethasone, a synthetic glucocorticoid, and of N,N-dimethylformamide on in vitro growth and differentiation and on proto-oncogene expression of human rhabdomyosarcoma cells were studied. RD/18 clone cells (derived from the embryonal rhabdomyosarcoma cell line RD) treated with 100 nM dexamethasone showed an almost complete block of differentiation: about 5% myosin-positive cells were observed after 2 weeks of culture in dexamethasone-supplemented differentiation medium, compared to 20% of untreated cultures. Dexamethasone also induced a 20-30% growth inhibition and a more flattened morphology. The treatment with N,N-dimethylformamide induced a significantly increased proportion of myosin-positive cells (reaching about 30%) and a 40% growth inhibition.Induction of differentiation inversely correlated with the levels of c-myc proto-oncogene expression: after a 2 week culture dexamethasone-treated cells showed the highest c-myc expression and N,N-dimethylformamidetreated cells the lowest. Culture conditions per se down-modulated c-erbBI and up-regulated c-jun expression, with no relationship to the differentiation pattern. Other proto-oncogenes were not expressed (c-sis, N-myc, c-mos, c-myb) or were not modulated (c-fos, c-raj).Therefore dexamethasone and N,N-dimethylformamide, both causing a decreased growth rate, showed opposing actions on myogenic differentiation and on c-myc proto-oncogene expression of human rhabdomyosarcoma cells.

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Section: Resultsmentioning

confidence: 99%

Uncoupling of growth inhibition and differentiation in dexamethasone-treated human rhabdomyosarcoma cells

Giovanni

Lollini²,

Dolcetti³

et al. 1993

Br J Cancer

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“…In the late 1980s it was shown that insulin increased the generation of PGE 2 and 6-oxo-PGF 1a in perfused rat muscle [49]. Pretreatment with PLA 2 inhibitors prevented this stimulation of PGE 2 and 6-oxo-PGF 1a generation and decreased PGF 2a release [50]. The cyclo-oxygenase inhibitors, indomethacin and ibuprofen, inhibited the insulin-induced stimulation of ribosomal RNA synthesis in L6 myoblasts [51].…”

Section: Cyclo-oxygenase-mediated Pathwaymentioning

confidence: 96%

Prostaglandylinositol cyclic phosphate (cPIP): a novel second messenger of insulin action. Comparative analysis of two kinds of ‘insulin mediators’

Shashkin

Wasner

Ortmeyer

et al. 2001

Diabetes Metabolism Res

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Insulin induces a broad spectrum of effects over a wide time interval. It also stimulates the phosphorylation of some cellular proteins, while decreasing the state of phosphorylation of others. These observations indicate the presence of different, but not necessarily mutually exclusive, pathways of insulin action. One well-known pathway represents a phosphorylation cascade initiated by the tyrosine kinase activity of the insulin receptor followed by involvement of different MAP-kinases. Another pathway suggests the existence of low molecular weight insulin mediators whose synthesis and/or release is initiated by insulin. Comparable analysis of two kinds of insulin mediators, namely inositolphosphoglycans and prostaglandylinositol cyclic phosphate (cPIP), has been carried out. It has been shown that the expression of a number of enzymes, such as phospholipase A(2), phospholipase C, cyclo-oxygenase and IRS-1-like enzyme, could regulate the biosynthesis of cPIP in both normal and diabetes-related conditions. Data on the activity of a key enzyme of cPIP biosynthesis termed cPIP synthase (IRS-1-like enzyme) in various monkey tissues before and twice during an euglycemic hyperinsulinemic clamp have been presented. It has been concluded that in vivo insulin increases cPIP synthase activity in both liver and subcutaneous adipose tissue of lean normal monkeys. It has been also suggested that abnormal production of cPIP could be related to several pathologies including glucocorticoid-induced insulin resistance and diabetic embryopathy. Further studies on cPIP and other types of insulin mediators are necessary to aid our understanding of insulin action.

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“…The radioactivity in 0.5 ml was determined using a 2000CA TriCarb liquid scintillation analyser. The rate of protein synthesis was calculated as dpm µg protein -1 h -1 as described (Southorn and Palmer, 1990). The protocol for DNA synthesis was the same as above except that methyl [ 3 H] thymidine (0.5 µCi) was added at the same time as LMF and left for 48 h. Protein was precipitated using ice-cold 5% trichloroacetic acid for 1 h at 4˚C.…”

Section: Precursor Incorporationmentioning

confidence: 99%

Effect of a tumour-produced lipid-mobilizing factor on protein synthesis and degradation

Islam-Ali

Tisdale

2001

Br J Cancer

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Treatment of murine myoblasts, myotubes and tumour cells with a tumour-produced lipid mobilizing factor (LMF), caused a concentration-dependent stimulation of protein synthesis, within a 24 h period. There was no effect on cell number or [ 3 H] thymidine incorporation, but a similar concentration-dependent stimulation of 2-deoxyglucose uptake. LMF produced an increase in intracellular cyclic AMP levels, which was linearly (r 2 = 0.973) related to the increase in protein synthesis. The effect of LMF was attenuated by the adenylate cyclase inhibitor MDL 12330A , and was additive with the stimulation produced by forskolin. Both propranolol (10 μM) and the specific β 3 -adrenergic receptor antagonist SR 59230A (10 –5 M), significantly reduced the stimulation of protein synthesis induced by LMF. Protein synthesis was also increased by 69% ( P = 0.006) in soleus muscles of mice administered LMF, while there was a 26% decrease in protein degradation ( P = 0.03). While LMF had no effect on the lysosomal enzymes, cathepsins B and L, there was a decrease in proteasome activity, as determined both by the ‘chymotrypsin-like’ enzyme activity, as well as expression of proteasome α-type subunits, determined by Western blotting. These results show that in addition to its lipid-mobilizing activity LMF also increases protein accumulation in skeletal muscle both by an increase in protein synthesis and a decrease in protein catabolism. © 2001 Cancer Research Campaign http://www.bjcancer.com

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Inhibitors of phospholipase A2 block the stimulation of protein synthesis by insulin in L6 myoblasts

Cited by 24 publications

References 14 publications

Uncoupling of growth inhibition and differentiation in dexamethasone-treated human rhabdomyosarcoma cells

Uncoupling of growth inhibition and differentiation in dexamethasone-treated human rhabdomyosarcoma cells

Prostaglandylinositol cyclic phosphate (cPIP): a novel second messenger of insulin action. Comparative analysis of two kinds of ‘insulin mediators’

Effect of a tumour-produced lipid-mobilizing factor on protein synthesis and degradation

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