scholarly journals Role of spermidine in the expression of late markers of adipose conversion Effects of growth hormone

1986 ◽  
Vol 239 (2) ◽  
pp. 363-370 ◽  
Author(s):  
E Z Amri ◽  
R Barbaras ◽  
A Doglio ◽  
C Dani ◽  
P Grimaldi ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Mrna Level ◽  
Fold Increase ◽  
Intracellular Concentration ◽  
Polyamine Content ◽  
Adipose Conversion ◽  
Highly Correlated ◽  
Glycerol 3 Phosphate Dehydrogenase

Confluent Ob1771 cells treated with an inhibitor of spermidine and spermine synthesis, methylglyoxyal bis(guanylhydrazone), were dependent on putrescine addition for the expression of glycerol-3-phosphate dehydrogenase and acyl-CoA synthetase, which behaved as late markers of adipose conversion. A similar dependence was observed with drug-treated Ob17MT18 and 3T3-F442A preadipocyte cells, but not with non-differentiating 3T3-C2 cells. Studies in drug-treated Ob1771 cells at the mRNA level showed that the parallel expression of mRNAs encoding for glycerol-3-phosphate dehydrogenase and an homologue of serine proteinases of Mr 28,000 [Cook, Groves, Min & Spiegelman (1985) Proc. Natl. Acad. Sci. U.S.A. 82, 6480-6484] was also dependent on putrescine addition. Double-isotope experiments with [14C]putrescine and [3H]spermidine, as well as analysis of the polyamine content in drug-treated Ob1771 cells under various conditions, demonstrate after putrescine addition that the expression of late markers of adipose conversion was highly correlated with a 2-fold increase in the intracellular concentration of spermidine. No correlation was observed with changes in the intracellular concentrations of putrescine and spermine. Long-term exposure of untreated Ob1771 cells to growth hormone, which led to the expression of late markers of adipose conversion [Doglio, Dani, Grimaldi & Ailhaud (1986) Biochem. J. 238, 123-129] was also accompanied by the same increase in spermidine concentration, which attained values identical with those determined in drug-treated cells supplemented with putrescine. This observation suggests that the permissive effect of growth hormone on the terminal differentiation of adipose cells might e related to changes in the intracellular concentration of spermidine.

scholarly journals Growth hormone regulation of the expression of differentiation-dependent genes in preadipocyte Ob1771 cells

1986 ◽  
Vol 238 (1) ◽  
pp. 123-129 ◽  
Author(s):  
A Doglio ◽  
C Dani ◽  
P Grimaldi ◽  
G Ailhaud
Keyword(s):  
Growth Hormone ◽  
Mrna Level ◽  
Protein A ◽  
Transcriptional Level ◽  
Hormone Regulation ◽  
Beta Actin ◽  
Adipose Conversion ◽  
Specific Mrnas ◽  
Actin Mrna ◽  
Glycerol 3 Phosphate Dehydrogenase

The adipose conversion of Ob1771 preadipocytes, during exposure to medium containing bovine serum and supplemented with growth hormone, is accompanied by the acquisition of phenotypic markers and the increased accumulation of specific mRNAs. The expression of lipoprotein lipase, and that of unidentified pOb24 and pGH3 mRNAs, are early events which are independent of growth hormone supplementation. By contrast, the late expression of mRNAs encoding for glycerol-3-phosphate dehydrogenase and p422 protein (a myelin-P2 homologue) and that of glycerol-3-phosphate dehydrogenase activity require the presence of growth hormone. The abundance of beta-actin mRNA does not change during differentiation. Runoff transcription by nuclei isolated from untreated or growth hormone-treated cells reveal little or no change in the rates of transcription of pOb24, pGH3 and beta-actin mRNAs. By contrast, the transcription rate of the p422 gene increases markedly (greater than 6-fold) in nuclei of growth hormone-treated cells. However, the p422 mRNA is more abundant than would be predicted by its nuclear transcription alone, suggesting, in Ob1771 cells exposed to growth hormone, that there is a post-transcriptional level of control. These results indicate that the permissive role of growth hormone during adipose cell differentiation is related to terminal events only and that its effects can be seen both at the protein and mRNA level. These results strongly suggest that an increased rate of specific transcription is primarily responsible for the accumulation of mRNAs during exposure to growth hormone.

scholarly journals Impact of earthquake-triggered landslides on catchment sediment yield

2015 ◽  
Vol 367 ◽  
pp. 291-296
Author(s):  
M. Vanmaercke ◽  
F. Obreja ◽  
J. Poesen
Keyword(s):  
Sediment Yield ◽  
Seismic Activity ◽  
Fold Increase ◽  
Sediment Concentration ◽  
Spatial And Temporal Variation ◽  
Strongly Correlated ◽  
Before And After ◽  
Sediment Export

Abstract. This study explores the role of seismic activity in explaining spatial and temporal variation in sediment export from the Siret basin in Romania. Based on long-term (>30 years) sediment export measurements for 38 subcatchments, we found that spatial variation in sediment yield (SY) is strongly correlated to the degree of seismic activity and catchment lithology. Combined, these factors explain 80% of the variation in SY. To investigate the role of earthquake-triggered landslides in explaining these correlations, we studied the temporal variability in sediment concentrations before and after the 7.4 Mw earthquake of 1977 for ten subcatchments. Despite the fact that this earthquake triggered many landslides, only one subcatchment showed a clear (3-fold) increase in sediment concentration per unit discharge after the earthquake. This shows that, although prolonged seismic activity strongly controls average SY, individual earthquakes do not necessarily affect sediment export at short timescales.

Short‐ and long‐term responsiveness to low dose growth hormone (GH) in adult GH deficiency: Role of GH receptor polymorphism

2019 ◽  
Vol 31 (4) ◽  
pp. e12692 ◽  
Author(s):  
Antonio Bianchi ◽  
Antonella Giampietro ◽  
Linda Tartaglione ◽  
Sabrina Chiloiro ◽  
Raffaella Gentilella ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Low Dose ◽  
Gh Deficiency ◽  
Gh Receptor ◽  
Adult Gh Deficiency ◽  
Short And Long Term ◽  
Receptor Polymorphism

scholarly journals Long-term erosion rates as a function of climate derived from the impact crater inventory

2019 ◽  
Vol 7 (2) ◽  
pp. 459-473 ◽  
Author(s):  
Stefan Hergarten ◽  
Thomas Kenkmann
Keyword(s):  
Impact Crater ◽  
Fold Increase ◽  
Regional Effect ◽  
Tropical Zone ◽  
Erosion Rates ◽  
Continental Scale ◽  
River Loads ◽  
The Impact

Abstract. Worldwide erosion rates seem to have increased strongly since the beginning of the Quaternary, but there is still discussion about the role of glaciation as a potential driver and even whether the increase is real at all or an artifact due to losses in the long-term sedimentary record. In this study we derive estimates of average erosion rates on the timescale of some tens of millions of years from the terrestrial impact crater inventory. This approach is completely independent from all other methods to infer erosion rates such as river loads, preserved sediments, cosmogenic nuclides, and thermochronometry. Our approach yields average erosion rates as a function of present-day topography and climate. The results confirm that topography accounts for the main part of the huge variation in erosion on Earth, but also identifies a significant systematic dependence on climate in contrast to several previous studies. We found a 5-fold increase in erosional efficacy from the cold regimes to the tropical zone and that temperate and arid climates are very similar in this context. Combining our results into a worldwide mean erosion rate, we found that erosion rates on the timescale of some tens of millions of years are at least as high as present-day rates and suggest that glaciation has a rather regional effect with a limited impact at the continental scale.

scholarly journals Insulin and Glucagon Impairments in Relation with Islet Cells Morphological Modifications Following Long Term Pancreatic Duct Ligation in the Rabbit – A Model of Non-insulin-dependent Diabete

2001 ◽  
Vol 2 (2) ◽  
pp. 101-112 ◽  
Author(s):  
J. Catala ◽  
M. Daumas ◽  
A. Pham Huu Chanh ◽  
B. Lasserre ◽  
E Hollande
Keyword(s):  
Pancreatic Duct ◽  
Islet Cells ◽  
Rabbit Model ◽  
Fold Increase ◽  
Pancreatic Duct Ligation ◽  
A Cells ◽  
Duct Ligation ◽  
Insulin Dependent

Plasma levels of glucose, insulin and glucagon were measured at various time intervals after pancreatic duct ligation (PDL) in rabbits. Two hyperglycemic periods were observed: one between 15–90 days (peak at 30 days of 15.1 ± 1.2mmol/l, p < 0.01), and the other at 450 days (11.2 ± 0.5 mmol/l, p < 0.02). The first hyperglycemic episode was significantly correlated with both hypoinsulinemia (41.8 ± 8pmol/l, r= –0.94, p < 0.01) and hyperglucagonemia (232 ± 21ng/l, r=0.95, p < 0.01). However, the late hyperglycemic phase (450 days), which was not accompanied by hypoinsulinemia, was observed after the hyperglucagonemia (390 days) produced by abundant immunostained A-cells giving rise to a 3-fold increase in pancreatic glucagon stores. The insulin and glucagon responses to glucose loading at 180, 270 and 450 days reflected the insensitivity of B- and A-cells to glucose. The PDL rabbit model with chronic and severe glycemic disorders due to the predominant role of glucagon mimicked key features of the NIDDM syndrome secondary to exocrine disease.

scholarly journals Adipose cell differentiation: evidence for a two-step process in the polyamine-dependent Ob1754 clonal line

1986 ◽  
Vol 238 (1) ◽  
pp. 115-122 ◽  
Author(s):  
E Z Amri ◽  
C Dani ◽  
A Doglio ◽  
J Etienne ◽  
P Grimaldi ◽  
...  
Keyword(s):  
Lipoprotein Lipase ◽  
Mrna Level ◽  
Growth Arrest ◽  
Clonal Line ◽  
Adipose Cell ◽  
Step Process ◽  
Late Emergence ◽  
Adipose Conversion ◽  
Early Expression ◽  
Glycerol 3 Phosphate Dehydrogenase

A subclone of preadipocyte Ob17 cells has been isolated (Ob1754 clonal line). Confluent Ob1754 cells treated with an inhibitor of spermidine and spermine synthesis, methylglyoxal bis(guanylhydrazone), were totally dependent upon putrescine addition for the expression of glycerol-3-phosphate dehydrogenase which behaved as a late marker of adipose conversion. Under these conditions, the early expression of lipoprotein lipase during growth arrest remained unchanged. Studies at the mRNA level showed that the expression of unidentified pOb24 and pGH3 mRNAs, which was parallel to that of lipoprotein lipase, is independent of polyamine addition whereas the late emergence of glycerol-3-phosphate dehydrogenase mRNA was putrescine-dependent and co-ordinated with the expression of pAL422 mRNA encoding for a myelin-P2 homologue [Bernlohr, Angus, Lane, Bolanowski & Kelly (1984) Proc. Natl. Acad. Sci. U.S.A. 81, 5468-5472]. The appearance of lipoprotein lipase preceded DNA synthesis and post-confluent mitoses which were both putrescine-dependent and which took place before the appearance of glycerol-3-phosphate dehydrogenase. Thus the adipose conversion of Ob1754 cells involves the expression of at least two separate sets of markers which are differently regulated.

Differential Effects of Protein Disulfide Isomerase (PDI) Inhibitors On the Expression of Tissue Factor Procoagulant Activity (TF PCA) by AML Blasts

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1112-1112
Author(s):  
Cornelia Fischer ◽  
Brigitte Spath ◽  
Ali Amirkhosravi ◽  
Walter Fiedler ◽  
Carsten Bokemeyer ◽  
...  
Keyword(s):  
Critical Role ◽  
Leukemic Cell ◽  
Fold Increase ◽  
Myelogenous Leukemia ◽  
Short Term ◽  
Short Term Treatment ◽  
Hl60 Cells ◽  
Short Term Exposure

Abstract Abstract 1112 Acute myelogenous leukemia (AML) may be complicated by DIC. TF plays a critical role in AML-associated coagulopathy, and induction of apoptosis significantly increases TF PCA on leukemic blasts, mainly via phosphatidylserine (PS) membrane exposure. However, PDI, a thiol isomerase with oxidoreductase and chaperone activity, has also been implicated in cellular TF regulation. Particularly, PDI inhibitors have been shown to exert antithrombotic activity in animal models. Besides its predominant localization in the endoplasmic reticulum, PDI is present on cell surfaces, where it may represent a promising therapeutic target. We investigated the effect of PDI inhibitors on the expression of TF PCA by leukemic HL60 and THP1 cells to explore their potential as anticoagulant drugs for the prevention and/or treatment of AML-associated DIC. Using a fluorescence-based insulin reduction assay, we confirmed inhibition of recombinant human PDI by bacitracin and quercetin-3-rutinoside (also known as rutin and recently shown to be a specific PDI inhibitor) with IC50 values of 0.6 mM and 14 μM, respectively, showing >95% inhibition at 1 mM (bacitracin) and 50 μM (rutin). Significant insulin reductase activity was observed on HL60 cells, and this activity was inhibited by 75% and 49% using 1 mM bacitracin and 100 μM rutin, respectively, suggesting the presence of additional, PDI-independent thiol isomerase activity. Short-term treatment with 100 μM rutin for 15 min also inhibited TF PCA on HL60 cells by 37%. Importantly, the inhibitory effect of rutin on cell-associated PDI and TF activity was completely abolished by cell washing, confirming previous evidence that rutin is a reversible PDI inhibitor. When HL60 cells were exposed to rutin (100 μM) for 24 hrs, cell-associated TF PCA was increased 2.3-fold (P<0.01), an effect that was accompanied by enhanced PS exposure, as assessed by annexin V-FITC binding (positive cells, 32±11 vs. 10±4%; P<0.01), and increased PCA of cellular microparticles (MPs) isolated from culture supernatants, as evidenced by the thrombin generation parameters lag phase (LP, 14±1 vs. 19±4 min), peak thrombin (PT, 55±17 vs. 22±14 nM), and area under the curve (AUC, 1193±329 vs. 476±347 nM*min; P<0.01). Interestingly, treatment with 100 μM rutin also resulted in a 1.7-fold increase in total cellular TF antigen (P=0.07). The effects of long-term incubation with bacitracin (1 mM) were even more pronounced, involving an 8.3-fold and 4.6-fold increase in cell-associated TF PCA and total cellular TF antigen, respectively. PS exposure (45±9%) and shedding of procoagulant MPs (LP, 7±1 min; PT, 175±49 nM; AUC, 2756±402 nM*min) were also significantly increased. While neither short-term nor long-term exposure to rutin affected TF PCA on THP1 cells, co-incubation with rutin dose-dependently (10–100 μM) inhibited daunorubicin-induced TF PCA in this cell model, an effect that could not be explained by decreased PS exposure. Importantly, both the reaction pattern of HL60 and that of THP1 cells were reproduced ex vivo using myeloblasts from AML patients. In summary, our findings suggest a highly complex and context-dependent role of PDI in leukemic-cell TF PCA expression. While short-term exposure to rutin can reversibly inhibit both PDI and TF activity, long-term exposure may result in significantly increased cellular TF PCA and MP shedding, pointing to a possible role of PDI in PS homeostasis, cytoskeleton rearrangement, and/or TF recycling. In addition, induction of leukemic-cell apoptosis and necrosis by cytotoxic drugs, which is associated with an early loss in membrane integrity and enhanced accessibility of cytoplasmic enzymes, may involve an additional role of (intracellular) PDI in the efficient presentation of TF PCA by AML blasts. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Evidence that mammalian phosphatidylinositol transfer protein regulates phosphatidylcholine metabolism

1998 ◽  
Vol 335 (1) ◽  
pp. 175-179 ◽  
Author(s):  
Marie E. MONACO ◽  
Richard J. ALEXANDER ◽  
Gerry T. SNOEK ◽  
Nancy H. MOLDOVER ◽  
Karel W. A. WIRTZ ◽  
...  
Keyword(s):  
Physiological Role ◽  
Fold Increase ◽  
Transfer Protein ◽  
Antisense Mrna ◽  
Cell Clones ◽  
Phosphatidylinositol Transfer

Phosphatidylinositol transfer proteins (PITPs) and their yeast counterpart (SEC14p) possess the ability to bind phosphatidylinositol (PtdIns) and transfer it between membranes in vitro. However, the biochemical function of these proteins in vivo is unclear. In the present study, the physiological role of PITP was investigated by determining the biochemical consequences of lowering the cellular content of this protein. WRK-1 rat mammary tumour cells were transfected with a plasmid containing a full-length rat PITPα cDNA inserted in the antisense orientation and the resultant cell clones were analysed. Three clones expressing antisense mRNA for PITPα were compared with three clones transfected with the expression vector lacking the insert. The three antisense clones had an average of 25% less PITPα protein than control clones. Two of the three antisense clones also exhibited a decreased rate of growth. All three antisense clones exhibited a significant decrease in the incorporation of labelled precursors into PtdCho during a 90-min incubation period. Under the same conditions, however, there was no change in precursor incorporation into PtdIns. Further experimentation indicated that the decrease in precursor incorporation seen in antisense clones was not due to an increased rate of turnover. When choline metabolism was analysed more extensively in one control (2-5) and one antisense (4-B) clone using equilibrium-labelling conditions (48 h of incubation), the following were observed: (1) the decrease in radioactive labelling of PtdCho seen in short-term experiments was also observed in long-term experiments, suggesting that the total amount of PtdCho was lower in antisense-transfected clones (this was confirmed by mass measurements); (2) a similar decrease was seen in cellular sphingomyelin, lysoPtdCho and glycerophosphorylcholine; (3) an average two-fold increase in cellular phosphorylcholine was observed in the antisense-transfected clone; (4) cellular choline was, on average, decreased; and (5) cellular CDPcholine was not significantly altered.

scholarly journals Requirement and role of arachidonic acid in the differentiation of pre-adipose cells

1989 ◽  
Vol 257 (2) ◽  
pp. 389-397 ◽  
Author(s):  
D Gaillard ◽  
R Négrel ◽  
M Lagarde ◽  
G Ailhaud
Keyword(s):  
Growth Hormone ◽  
Arachidonic Acid ◽  
Cyclic Amp ◽  
Adipose Conversion ◽  
Inositol Phospholipid ◽  
Glycerol 3 Phosphate Dehydrogenase ◽  
Triacylglycerol Accumulation ◽  
Exogenous Origin ◽  
Inositol Phospholipid Breakdown ◽  
Adipose Cells

The terminal adipose differentiation of Ob1771 cells, characterized by glycerol-3-phosphate dehydrogenase activity and triacylglycerol accumulation, was studied in serum-free hormone-supplemented medium containing growth hormone, tri-iodothyronine, insulin, transferrin and fetuin. Arachidonic acid was able to substitute for a crude adipogenic fraction isolated from fetal bovine serum but not for growth hormone or tri-iodothyronine. Arachidonic acid was also able to increase in a rapid and dramatic manner cyclic AMP production; moreover it was able to amplify the adipose conversion promoted by other agents elevating cyclic AMP concentrations and to induce inositol phospholipid breakdown. Both phorbol 12-myristate 13-acetate, a protein kinase C activator and ionomycin, a Ca2+-mobilizing agent, showed potent synergy with agents elevating cyclic AMP concentrations for the promotion of adipose conversion, whereas 8-bromo cyclic GMP and 4 alpha-phorbol 12,13-dibutyrate were ineffective. The triggering of both the cyclic AMP and inositol phospholipid pathways was accompanied by a single round of cell division, and within a few days all the cells became differentiated. Similar results were obtained, after exposure to arachidonic acid, with preadipose 3T3-F442A cells and with rat adipose precursor cells in primary culture. The availability of arachidonic acid from intracellular stores and/or of exogenous origin should play a major role for the onset of critical mitoses leading to terminal differentiation in pre-adipose cells.

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