scholarly journals Stimulation of adipose differentiation related protein (ADRP) expression by ibuprofen and indomethacin in adipocyte precursors and in adipocytes

1998 ◽  
Vol 330 (2) ◽  
pp. 803-809 ◽  
Author(s):  
Hong YE ◽  
Ginette SERRERO
Keyword(s):  
Adipocyte Differentiation ◽  
Nordihydroguaiaretic Acid ◽  
Cyclooxygenase Inhibitors ◽  
Related Protein ◽  
Lipoxygenase Inhibitors ◽  
Undifferentiated Cells ◽  
Dose Dependent Fashion ◽  
Adipose Differentiation ◽  
High Level ◽  
Stimulation Of

Adipose differentiation related protein (ADRP) is a 50 kDa protein expressed at high level in differentiated adipocytes. ADRP expression is very low in undifferentiated adipocytes and increases rapidly and dramatically as the cells undergo adipose differentiation. In the present study, we demonstrate that ADRP expression at the mRNA and protein level is stimulated in adipocyte precursor cells in a time- and dose-dependent fashion by treatment with cyclooxygenase inhibitors, particularly indomethacin and ibuprofen. Lipoxygenase inhibitors such as AA861 and nordihydroguaiaretic acid were ineffective. Stimulation of ADRP expression was observed with 10-5 M ibuprofen but maximal stimulation required a concentration of 3×10-4 M. Nuclear run-on experiments indicated that indomethacin or ibuprofen stimulated the transcription of the ADRP gene in undifferentiated adipocytes. In addition to stimulating the induction of ADRP in undifferentiated cells, ibuprofen and indomethacin also stimulated the level of ADRP mRNA and protein in differentiated adipocytes. These experiments provide new information on the regulation of ADRP, an early inducible gene in the adipocyte differentiation programme in adipocyte precursors and in adipocytes and identify a new target for cyclooxygenase inhibitor action during adipocyte differentiation.

scholarly journals Fundamental Concepts in the Assessment of Interaction of Biological Response Modifiers with other Agents

1992 ◽  
Vol 3 (suppl b) ◽  
pp. 60-68 ◽  
Author(s):  
William R Greco ◽  
Wlodzimierz E Dembinski
Keyword(s):  
Drug Exposure ◽  
Biological Response ◽  
Nordihydroguaiaretic Acid ◽  
Mouse Cell ◽  
Cyclooxygenase Inhibitors ◽  
Concentration Effect ◽  
Estimation Of Parameters ◽  
Surface Approach ◽  
Lipoxygenase Inhibitors

The universal response surface approach (URSA) was developed to assess the nature and intensity of drug interactions, ie, synergism. antagonism and additivity. URSA consists of fitting a concentration-effect surface to experimental data with maximum likelihood approaches, with the estimation of parameters, including: ID5os, concentration-effect slopes and the synergism-antagonism parameter α When α is positive, synergism is indicated, when α is negative, antagonism is indicated and when α is zero. additivity is indicated. URSA was applied to data from a set of 45 in vitro growth inhibition experiments with the L929 mouse cell line. The cytokine, tumour necrosis factor (TNF), was combined with one of nine eicosanoid synthesis inhibitors: indomethacin, Ro 20-5720, ibuprofen (cyclooxygenase inhibitors): nordihydroguaiaretic acid, nafazatrom, esculetin (lipoxygenase inhibitors): or BW-755C, p henidone, timegadine [cyclo- and lipoxygenase inhibitors). Five different schedules were used with various orders and durations of drug exposure. Examples of all three types of drug interaction were found for combinations of TNF with all three classes of drugs. The largest synergism found was for TNF plus BW-755C (α = 4.30±1.3 [SE]). In general, for each combination, the degree of synergism was greater for schedules in which cells were exposed to TNF before exposure to the other agent.

Studies on the roles of phospholipase A2 and eicosanoids in the regulation of corticotrophin secretion by rat pituitary cells in vitro

1991 ◽  
Vol 130 (1) ◽  
pp. 21-32 ◽  
Author(s):  
A. M. Cowell ◽  
R. J. Flower ◽  
J. C. Buckingham
Keyword(s):  
Arachidonic Acid ◽  
Platelet Activating Factor ◽  
Nordihydroguaiaretic Acid ◽  
Cyclooxygenase Inhibitors ◽  
Pituitary Cells ◽  
Lipoxygenase Inhibitor ◽  
Acth Secretion ◽  
Lipoxygenase Inhibitors ◽  
Prostaglandin F

ABSTRACT Dispersed anterior pituitary cells were used to investigate the possible roles of phospholipid metabolites released by phospholipase A2 (PLA2) in the control of immunoreactive ACTH (ir-ACTH) secretion in vitro. PLA2 (15 600–62 500 U/1), the PLA2 activator melittin (0·5–20 mg/l) and arachidonic acid (1 mmol/l) all produced increases in ir-ACTH release from the cells, whilst platelet-activating factor (PAF), prostaglandin F2α (PGF2α), the prostacyclin analogues iloprost and BW245C, the thromboxane A2 (TXA2) analogue U46619, and the leukotrienes LTB4 and LTC4 were ineffective in this respect. PGF2α (100 nmol/l and 1 μmol/l), iloprost (1 μmol/l) and BW245C (100 nmol/l and 1 μmol/l) depressed corticotrophin-releasing factor-41-induced ir-ACTH secretion, while the PAF antagonist BN52021 (10 and 100 μmol/l) and LTC4 (100 nmol/l and 1 μmol/l) had no discernable effects. The secretory responses of the cells to hypothalamic extracts (0·2 hypothalami/ml) and arachidonic acid (1 mmol/l) were generally unaffected by the cyclooxygenase inhibitors ibuprofen (10 and 100 μmol/l) and indomethacin (10 μmol/l), the TXA2 synthetase inhibitor imidazole (10 μmol/l–1 mmol/l), the lipoxygenase inhibitor nordihydroguaiaretic acid (10 and 100 μmol/l) and the dual cyclo-oxygenase/lipoxygenase inhibitors phenidone (1–100 μmol/l) and BW755C (10 and 100 μmol/l). They were, however, inhibited by the dual cyclo-oxygenase/lipoxygenase inhibitor eicosatetraynoic acid (10 and 100 μmol/l), which also blocks epoxygenase and PLA2 activity and by the cytochrome P450 inhibitor SKF-525A (1 mmol/l). The results suggest that the stimulatory effects of PLA2 and arachidonic acid on ir-ACTH secretion are not effected by products generated by the cyclo-oxygenase or lipoxygenase pathways but may be mediated by metabolites generated by the cytochrome P450 pathway. Journal of Endocrinology (1991) 130, 21–32

Stretch-stimulated surfactant synthesis is coordinated by the paracrine actions of PTHrP and leptin

2002 ◽  
Vol 283 (1) ◽  
pp. L130-L135 ◽  
Author(s):  
J. S. Torday ◽  
V. K. Rehan
Keyword(s):  
Pulmonary Surfactant ◽  
Feedback Loop ◽  
Related Protein ◽  
Phospholipid Synthesis ◽  
Alveolar Epithelial ◽  
Parathyroid Hormone Related Protein ◽  
Surfactant Production ◽  
Adipose Differentiation ◽  
Paracrine Actions ◽  
Stimulation Of

Intrauterine lung development, culminating in physiological pulmonary surfactant production by epithelial type II (TII) cells, is driven by fluid distension through unknown mechanisms. Differentiation of alveolar epithelial and mesenchymal cells is mediated by soluble factors like parathyroid hormone-related protein (PTHrP), a stretch-sensitive TII cell product. PTHrP stimulates pulmonary surfactant production by a paracrine feedback loop mediated by leptin, a soluble product of the mature lipofibroblast (LF). When LFs and TIIs are stretched in coculture, there is a fivefold increase in surfactant phospholipid synthesis that can be “neutralized” by inhibitors of PTHrP or leptin, implicating a paracrine feedback loop in this mechanism. Stretching LFs stimulates PTHrP binding (2.5-fold) and downstream stimulation of triglyceride uptake quantitatively (15–25%) due to upregulation of adipose differentiation-related protein expression. Stretching TII cells increases leptin stimulation of their surfactant phospholipid synthesis threefold, suggesting that retrograde signaling by leptin to TII cells is also stretch sensitive. We conclude that the effect of stretch on alveolar LF and TII differentiation is coordinated by PTHrP, leptin, and their receptors.

Kinetin-Mediated Stimulation of Accumulation of Buckwheat Flavonoids in the Dark

1983 ◽  
Vol 38 (9-10) ◽  
pp. 711-718 ◽  
Author(s):  
U. Margna ◽  
T. Vainjärv
Keyword(s):  
Anthocyanin Biosynthesis ◽  
Flavonoid Biosynthesis ◽  
Accumulation Rates ◽  
Sharp Rise ◽  
Short Treatment ◽  
Exogenous Substrate ◽  
Percent Increase ◽  
High Level ◽  
Fold Stimulation ◽  
Stimulation Of

A short treatment of excised buckwheat cotyledons with a solution of kinetin lead to an up to 9-fold stimulation of anthocyanin biosynthesis, to an about 50 percent increase in the accumula­tion of rutin, and to an about 30 percent increase, on the average, in the accumulation of C-glycosylflavones in the treated material during its posttreatment incubation in the dark. When the treated cotyledons were incubated in a solution of ʟ--phenylalanine anthocyanin accumulation in the dark practically attained the same high level as it was observed in the illuminated cotyledons fed with exogenous ʟ--phenylalanine. In experiments with l4C-labelled L-phenylalanine kinetin induced a sharp rise in the labelling (resp. in the utilization of exogenous substrate for biosynthesis) of anthocyanins and rutin in the dark and a slight increase in the radioactivity of C-glycosylflavones. Similar labelling changes occurred in the illuminated cotyledons. However, both kinetin and light still more effectively promoted biosynthetic use of the endogenous sub­strate. As a result the relative portion of flavonoids formed from exogenous L-phenylalanine under these conditions showed a decrease as compared with the ratio of precursor use in the un­treated cotyledons. The results show that low accumulation rates of anthocyanins and other flavo­noids in the dark are conditioned by the limited access of substrate (ʟ--phenylalanine) molecules to the flavonoid enzymes lending further support to the idea that flavonoid biosynthesis is normally controlled at the substrate rather than at the enzymic level.

scholarly journals α-Conotoxins and α-Cobratoxin Promote, while Lipoxygenase and Cyclooxygenase Inhibitors Suppress the Proliferation of Glioma C6 Cells

Marine Drugs ◽  
2021 ◽  
Vol 19 (2) ◽  
pp. 118
Author(s):  
Tatiana I. Terpinskaya ◽  
Alexey V. Osipov ◽  
Elena V. Kryukova ◽  
Denis S. Kudryavtsev ◽  
Nina V. Kopylova ◽  
...  
Keyword(s):  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Glioma Cells ◽  
Nordihydroguaiaretic Acid ◽  
C6 Glioma ◽  
Cyclooxygenase Inhibitors ◽  
C6 Glioma Cells ◽  
C6 Cells ◽  
Lipoxygenase Inhibitor ◽  
Glioma C6

Among the brain tumors, glioma is the most common. In general, different biochemical mechanisms, involving nicotinic acetylcholine receptors (nAChRs) and the arachidonic acid cascade are involved in oncogenesis. Although the engagement of the latter in survival and proliferation of rat C6 glioma has been shown, there are practically no data about the presence and the role of nAChRs in C6 cells. In this work we studied the effects of nAChR antagonists, marine snail α-conotoxins and snake α-cobratoxin, on the survival and proliferation of C6 glioma cells. The effects of the lipoxygenase and cyclooxygenase inhibitors either alone or together with α-conotoxins and α-cobratoxin were studied in parallel. It was found that α-conotoxins and α-cobratoxin promoted the proliferation of C6 glioma cells, while nicotine had practically no effect at concentrations below 1 µL/mL. Nordihydroguaiaretic acid, a nonspecific lipoxygenase inhibitor, and baicalein, a 12-lipoxygenase inhibitor, exerted antiproliferative and cytotoxic effects on C6 cells. nAChR inhibitors weaken this effect after 24 h cultivation but produced no effects at longer times. Quantitative real-time polymerase chain reaction showed that mRNA for α4, α7, β2 and β4 subunits of nAChR were expressed in C6 glioma cells. This is the first indication for involvement of nAChRs in mechanisms of glioma cell proliferation.

Adipocyte differentiation of 3T3-L1 preadipocytes is dependent on lipoxygenase activity during the initial stages of the differentiation process

2003 ◽  
Vol 375 (3) ◽  
pp. 539-549 ◽  
Author(s):  
Lise MADSEN ◽  
Rasmus K. PETERSEN ◽  
Morten B. SØRENSEN ◽  
Claus JØRGENSEN ◽  
Philip HALLENBORG ◽  
...  
Keyword(s):  
Adipocyte Differentiation ◽  
Critical Evaluation ◽  
Nordihydroguaiaretic Acid ◽  
Whole Body ◽  
Transcriptional Networks ◽  
Peroxisome Proliferator ◽  
The Novel ◽  
Differentiation Process ◽  
Peroxisome Proliferator Activated Receptor ◽  
Brown Adipose

Adipocytes play a central role in whole-body energy homoeostasis. Complex regulatory transcriptional networks control adipogensis, with ligand-dependent activation of PPARγ (peroxisome proliferator-activated receptor γ) being a decisive factor. Yet the identity of endogenous ligands promoting adipocyte differentiation has not been established. Here we present a critical evaluation of the role of LOXs (lipoxygenases) during adipocyte differentiation of 3T3-L1 cells. We show that adipocyte differentiation of 3T3-L1 preadipocytes is inhibited by the general LOX inhibitor NDGA (nordihydroguaiaretic acid) and the 12/15-LOX selective inhibitor baicalein. Baicalein-mediated inhibition of adipocyte differentiation was rescued by administration of rosiglitazone. Treatment with baicalein during the first 4 days of the differentiation process prevented adipocyte differentiation; supplementation with rosiglitazone during the same period was sufficient to rescue adipogenesis. Accordingly, we demonstrate that adipogenic conversion of 3T3-L1 cells requires PPARγ ligands only during the first 4 days of the differentiation process. We show that the baicalein-sensitive synthesis of endogenous PPARγ ligand(s) increases rapidly upon induction of differentiation and reaches a maximum on days 3–4 of the adipocyte differentiation programme. The conventional platelet- and leucocyte-type 12(S)-LOXs and the novel eLOX-3 (epidermis-type LOX-3) are expressed in white and brown adipose tissue, whereas only eLOX-3 is clearly expressed in 3T3-L1 cells. We suggest that endogenous PPARγ ligand(s) promoting adipocyte differentiation are generated via a baicalein-sensitive pathway involving the novel eLOX-3.

scholarly journals Increased intracellular cyclic adenosine monophosphate inhibits T lymphocyte-mediated cytolysis by two distinct mechanisms.

1988 ◽  
Vol 167 (6) ◽  
pp. 1963-1968 ◽  
Author(s):  
L S Gray ◽  
J Gnarra ◽  
E L Hewlett ◽  
V H Engelhard
Keyword(s):  
Cholera Toxin ◽  
T Lymphocyte ◽  
Pertussis Toxin ◽  
Target Cell ◽  
Cyclic Adenosine Monophosphate ◽  
Second Messenger ◽  
Adenosine Monophosphate ◽  
Dose Dependent Fashion ◽  
Dose Dependent ◽  
Stimulation Of

Cholera toxin (CT), but not pertussis toxin (PT), treatment of cloned murine CTL inhibited target cell lysis in a dose-dependent fashion. The effects of CT were mimicked by forskolin and cyclic adenosine monophosphate (cAMP) analogues. Inhibition of cytotoxicity by CT and cAMP analogs was mediated in part by attenuation of conjugate formation. Additionally, both CT and cAMP analogs blocked the increase in intracellular Ca2+ induced by stimulation of the TCR complex by mAbs. These findings indicate that cAMP inhibits the activity of CTL by two distinct mechanisms and suggests a role for this second messenger in CTL-mediated cytolysis.

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