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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In contrast to previous studies, Parker et al. (Diabetes (1989) 38, 1123) have recently found that isolated rat adipocytes alone were unable to synthesize prostaglandins (PG) and that the PG measured in adipocyte suspensions were due to contaminating non-adipocyte cells. In the present study the capacity of adipocytes to produce PGE2 has further been explored. Preparations of isolated rat adipocytes were extensively washed in order to get rid of contaminating cells. The released PGE2 was measured by radioimmunoassay (RIA) after high-performance liquid chromatography (HPLC) separation. We found that after repetitive washing (up to 20 times) the isolated adipocytes were still able to synthesize PGE2 and this process was fully activatable by epinephrine, which indicates that pure adipocytes, themselves, are able to produce PGE2. However, addition of non-adipocyte material (from the adipose tissue) to 'pure' adipocytes (washed 10 times) enhanced the PGE2 synthesis significantly (P less than 0.001) as compared to 'pure' adipocytes alone. Thus, some kind of synergy exists between adipocytes and non-adipocyte cells in the adipose tissue in respect to PG formation. Some regulatory aspects of PG synthesis in 'pure' adipocytes were also investigated. Phospholipase A2 (2 U/ml) enhanced PGE2 synthesis significantly (119 +/- 21 to 658 +/- 85 pg/10(6) cells, P less than 0.001) without affecting lipolysis (glycerol release). The combined effect of epinephrine (5 microM) and phospholipase A2 (2 U/ml) on PGE2 formation was almost additive. Insulin inhibited the epinephrine-induced PG formation (P less than 0.01) but had no effects on the action induced by phospholipase A2.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Cell Endocrinol 1992 May
PMID:Biosynthetic capacity and regulatory aspects of prostaglandin E2 formation in adipocytes. 152 16

Inflammatory mediators promote the synthesis and secretion of prostaglandin (PG) mediators in airway epithelial cells. In this study, we examined the topographic and kinetic profile of PG secretion in canine tracheal epithelial cells harvested from the tracheal posterior membrane (PM) and those obtained from the immediately anterior cartilage-associated membrane (CM). Primary cultures of tracheal epithelial cells obtained from 23 disease-free dogs were grown to confluence in serum-enriched medium. Cells then were incubated in serum-free medium for 1 h and stimulated with 10(-7) to 10(-5) M bradykinin. Baseline secretion of PGE2 was similar to both PM and CM cells; however, PM cells secreted greater concentrations in both PGI2 (measured as 6-keto-PGF1 alpha) (1,269 +/- 160 versus 775 +/- 91 pg/10(6) cells, P less than 0.01) and PGF2 alpha (436 +/- 54 versus 234 +/- 45 pg/10(6) cells, P less than 0.002) compared with CM cells. Bradykinin (BK) stimulation caused substantial secretion in less than or equal to 20 min of PGE2 and 6-keto-PGF1 alpha from PM but not CM cells: after stimulation with 10(-6) M BK, 6-keto-PGF1 alpha secretion was 348 +/- 74% in PM cells versus 157 +/- 18% of baseline secretion in CM cells (P less than 0.005); PGE2 secretion was 310 +/- 53% in PM cells versus 163 +/- 15% of baseline secretion in CM cells (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
Am J Respir Cell Mol Biol 1992 Apr
PMID:Topographic distribution of prostaglandin secretion caused by bradykinin in canine tracheal epithelial cells. 155 Jun 82

T lymphocytes from T. cruzi infected mice susceptible to the development of myocarditis altered the contractility of normal mouse atria in vitro. While lymphocytes obtained from normal mice had no effect, lymphocytes from T. cruzi-infected mice cultured with normal atria induced negative or positive inotropic effects depending upon the post-infection period; negative inotropism was induced by lymphocytes obtained from animals at 1 to 4 weeks post-infection, and positive inotropism was induced by lymphocytes taken at 7 to 14 weeks post-infection. These effects were mediated by soluble factors as evidenced by the ability of lymphocyte culture supernatants to alter contractility. Cell enrichment experiments indicated that T lymphocytes rather than B lymphocytes were responsible for these inotropic effects. Lyt(2+)-enriched T lymphocytes were found to be responsible for triggering the negative inotropic effect at 3 weeks post-infection when myocarditis was less intense, whereas Lyt1(+)-enriched T lymphocytes induced the positive inotropic effect at 8 weeks after T. cruzi infection when myocarditis was severe. Furthermore, inhibitors of the cyclooxygenase pathway of arachidonic acid metabolism blunted the negative inotropic effect while inhibitors of lipoxygenase pathway inhibited the positive inotropic effect. PGE2 was found to be spontaneously released by Lyt(2+)-enriched T cells obtained at 3 weeks post-infection while LTC4 was released by atria cultured in the presence of Lyt 1+ T cells obtained at 8 weeks post-infection. In conclusion, these findings suggest that infiltrating T lymphocytes may contribute to myocardial dysfunction during T. cruzi infection by releasing or inducing the release of harmful arachidonic acid metabolites such as PGE2 and LTC4 which alter normal cardiac function.
J Mol Cell Cardiol 1992 Jan
PMID:T lymphocytes from T. cruzi-infected mice alter heart contractility: participation of arachidonic acid metabolites. 156 33

Recent evidence suggests that the steady state level of prostaglandin (PG) endoperoxide synthase (PES) might regulate long term increases in PG synthesis, but the mechanism(s) regulating PES gene expression remains unclear. The present experiments investigated the regulation of PES expression in quiescent mesangial cells treated with serum. Serum induced time-dependent increases in PES steady state mRNA, protein level, and enzyme activity. Both the kinetics and cycloheximide sensitivity of PES mRNA induction suggest that PES was induced as a member of the delayed-early gene set. Beta-adrenergic-mediated cAMP accumulation was similar in Go and cycling cells, suggesting that the increase in PES expression did not reflect global up-regulation of signaling cascades in serum-treated cells. Three lines of evidence suggest that protein kinase-C (PKC) mediates serum-stimulated PES gene expression: 1) 12-tetradecanoyl phorbol 13-acetate mimicked the serum response; 2) PES gene expression by serum was attenuated in cells depleted of PKC; and 3) a PKC inhibitor, sangivamycin, blocked serum-stimulated PES gene induction. In addition, the ability of dexamethasone to block serum-induced PES enzyme activity without affecting the increase in PES mRNA points to posttranscriptional mechanisms of regulation. In summary, we conclude that in glomerular mesangial cells the PES gene is inducible, not constitutive, and that expression of this gene in Go cells is induced by serum and results in chronic elevations of PGE2. These findings are consistent with the hypothesis that differential regulation of PES gene expression might play a role in diverse cellular responses, such as mitogenesis and inflammation.
Mol Endocrinol 1991 Mar
PMID:Regulation of prostaglandin endoperoxide synthase gene expression in cultured rat mesangial cells: induction by serum via a protein kinase-C-dependent mechanism. 165 96

In intact NIH 3T3 murine fibroblasts, prostaglandins (PGs) F2 alpha and E2 induce dose-dependent stimulation of inositol monophosphate generation. PGF2 alpha is greater than 50-fold more potent than PGE2 in eliciting this response. In streptolysin O-permeabilized NIH 3T3 cells, PGF2 alpha and PGE2 induced dose-dependent accumulations of inositol bis- and trisphosphates, which were dependent on the presence of the guanine nucleotide guanosine-5'-O-(3-thio)triphosphate (GTP gamma S) (10 microM). Pretreatment of cells for 16 hr with 100 nM PGF2 alpha resulted in a significant reduction of not only subsequent PGF2 alpha- and PGE2-induced but also GTP gamma S-induced stimulation of inositol phosphate formation in permeabilized cells. PGF2 alpha-induced accumulation of inositol phosphates was partially inhibited by pretreatment with pertussis toxin (1 microgram/ml, 4 hr). The inhibition by pertussis toxin was small but was not related to cyclic AMP formation, because forskolin, which activates adenylate cyclase, did not mimic pertussis toxin-induced inhibition. In the same cell line, PGF2 alpha and PGE2 induced a dose-dependent accumulation of cAMP and a dose-dependent potentiation of 0.5 microM forskolin-stimulated cAMP formation. PGF2 alpha and PGE2 were almost equipotent in eliciting both responses. However, PGF2 alpha was less efficacious than PGE2 and, in the presence of forskolin, PGF2 alpha at 10 microM induced an inhibitory effect on cAMP accumulation. Such inhibition may be related to PGF2 alpha-mediated phospholipase C activation and subsequent stimulation of protein kinase C, because the phorbol ester phorbol 12-myristate-13-acetate, which directly activates protein kinase C, also inhibited forskolin- and PGE2-induced cAMP accumulation. Pretreatment with PGF2 alpha for 16 hr did not reduce subsequent stimulation of cAMP accumulation by PGF2 alpha or PGE2. The results indicate that in NIH 3T3 cells two receptors for PGs are present, one that couples to adenylate cyclase, probably through Gs, and does not exhibit selectivity between PGF2 alpha and PGE2 and a second receptor that couples to phospholipase C through a guanine nucleotide-binding protein that is not sensitive to pertussis toxin pretreatment. The latter shows at least 40-fold selectivity towards PGF2 alpha over PGE2. Because long treatment with PGF2 alpha resulted in desensitization of the GTP gamma S-induced response, it is possible that long exposure to PGF2 alpha may down-regulate the guanine nucleotide-binding involved in phospholipase C signal transduction.
Mol Pharmacol 1991 Nov
PMID:Prostaglandin receptors in NIH 3T3 cells: coupling of one receptor to adenylate cyclase and of a second receptor to phospholipase C. 165 2

We have developed an alternative method for examining equine tracheal epithelial arachidonic acid (AA) metabolism that utilizes strips of pseudostratified columnar epithelium attached to a layer of elastic tissue 80 to 130 microns thick. We compared the responses of this preparation with those of enzymatically dispersed suspensions of tracheal epithelium obtained from the same animal. Strips incubated with [3H]AA incorporated 40.8 +/- 3.6% of added radioactivity and released 2.55 +/- 0.23% of incorporated radioactivity when stimulated with 5 microM A23187. Values for the cell suspension were 59.6 +/- 1.6% and 1.90 +/- 0.08%, respectively. Stimulation with 50 microM histamine or bradykinin resulted in significant release of free [3H]AA only from the strips. High-performance liquid chromatography radioactivity profiles of eicosanoids released following stimulation with 5 microM A23187 demonstrated peaks that coeluted with free AA, prostaglandin (PG) E2, and PGF2 alpha for the strips, and free AA, leukotriene B4, and 5-HETE for the cell suspensions. The absence of PGE2 production by cell suspensions was confirmed by assaying immunoreactive PGE2 in supernatants from unlabeled strips and suspensions stimulated with 5 microM A23187. Epithelial strips produced 10.3 +/- 1.3 ng PGE2/ml supernatant, whereas 5 x 10(6) cells in suspension produced less than 100 pg/ml. Despite the lack of PG production by the cell suspensions, immunocytochemical staining with an anti-PGH synthase antibody demonstrated the presence of PGH synthase in epithelial cells of both preparations. These data indicate that, in contrast to epithelial cell suspensions, epithelial strips synthesize cyclooxygenase metabolites and respond to peptide agonists.(ABSTRACT TRUNCATED AT 250 WORDS)
Am J Respir Cell Mol Biol 1992 Jan
PMID:Epithelial strips: an alternative technique for examining arachidonate metabolism in equine tracheal epithelium. 172 92

Arachidonic acid (AA) metabolism was studied in freshly isolated type II alveolar epithelial cells of rabbits. Substantial basal secretion of prostanoids with predominance of prostaglandin (PG) I2 was noted. Challenge with the calcium ionophore A23187 resulted in a time- and dose-dependent increase in the generation of all AA cyclooxygenase products to severalfold values following the rank order of 12-heptadecatrienoic acid (12-HHT) greater than PGI2 greater than PGE2 greater than or equal to thromboxane A2 greater than PGF2 alpha approximately PGD2. Even larger augmentation of prostanoid generation was evoked by challenge with free exogenous AA. Generation of the different AA cyclooxygenase products was inhibited by acetylsalicylic acid with IC50 in the range between 250 and 500 microM. In addition to the prostanoid release, ionophore-challenged type II pneumocytes liberated substantial amounts of AA lipoxygenase products with leukotriene (LT) B4 greater than 15-hydroxyeicosatetraenoic acid (HETE) greater than 12-HETE greater than 5-HETE. Generation of LTs and HETEs was markedly increased upon simultaneous disposal of free exogenous AA. No omega-oxidation of LTB4 was noted, and no evidence for secretion of intact LTA4 was obtained. The epithelial cells displayed avid uptake of exogenously offered LTA4 with subsequent enzymatic conversion to LTB4. Co-stimulation of pneumocytes with neutrophils (PMN) resulted in an amplification of LTB4 generation, paralleled by a decrease in nonenzymatic decay products of PMN-derived LTA4; both phenomena were dose dependent on the pneumocyte-PMN ratio.(ABSTRACT TRUNCATED AT 250 WORDS)
Am J Respir Cell Mol Biol 1992 Jan
PMID:Type II alveolar epithelial eicosanoid metabolism: predominance of cyclooxygenase pathways and transcellular lipoxygenase metabolism in co-culture with neutrophils. 172 1

Interleukin 1 (IL-1) is a major immunoregulatory protein released by macrophages with many host defense related properties. That IL-1 has been found in the invertebrates attests to its importance in homeostasis. The first step in comparing the vertebrate protein to its invertebrate correlate is to purify the protein to study. We have purified to homogeneity IL-1 isolated from the coelomic fluid of the starfish Asterias forbesi. The IL-1 had isoelectric points of 7.4, 5.4 and 4.8. The pI 4.8 species had a molecular weight of 22,000 and the pI 7.4 and 5.4 species both had Mr of 17,000. Higher Mr forms were also found. These molecules were biologically active in the human melanoma A375 cytotoxicity assay for IL-1, and were also able to stimulate murine dermal fibroblast proliferation, protein synthesis, and PGE2 production. The pI 4.8 and 5.4 forms were purified to homogeneity and the amino acid composition was determined. The pI 4.8 and 5.4 species were purified more than 200-fold to specific activities of 3 x 10(6) and 1 x 10(6) units mg-1, respectively. The pI 7.4 form was isolated and partial N-terminal sequence analysis was performed. The similarities of molecular weight, isoelectric points and biological properties between vertebrate and invertebrate IL-1 show that it is an important, evolutionarily stable host defense molecule.
Mol Immunol 1991 Jun
PMID:Purification and biochemical characterization of an invertebrate interleukin 1. 186 78

16,16-Dimethyl PGE2 (dmPGE2) is known to protect against cellular damage in various tissues. Histological and biochemical approaches were used to examine the effect of this prostaglandin on hepatocellular damage in an experimental Reye's syndrome model produced in rats by 4-pentenoic acid. Chronic intraperitoneal administration of 4-pentenoic acid induced an accumulation of fatty droplets throughout the hepatic lobules along with mitochondrial abnormalities including swelling, disappearance of christae, and heterogeneity of matrix. These abnormalities were more intense in the marginal zone and successively decreased nearer to the central vein. Such hepatic abnormalities were markedly reduced by the combined administration of dmPGE2 with 4-pentenoic acid. Biochemical examination confirmed that dmPGE2 was able to inhibit the accumulation of hepatic triglyceride seen after the treatment with 4-pentenoic acid alone. These results indicated that dmPGE2 can prevent characteristic hepatocellular damage in this experimental Reye's syndrome model, suggesting that the involvement of prostaglandins should be taken into account in discussing the etiology and management of this syndrome.
Exp Mol Pathol 1991 Oct
PMID:Prevention of 4-pentenoic acid-induced liver injury in rats by 16,16-dimethyl PGE2. 193 11

The contribution of prostanoids to the change in coronary flow induced by hypoxia was examined in Langendorff-perfused rat heart. In the coronary effluent, 5 prostanoids, i.e., prostaglandins (PGs) D2, E2, and F2 alpha, 6-keto PGF1 alpha and thromboxane (TX) B2, were quantified by GC/MS, whereas PGA2, B2, and E1 were not detected under any conditions. During hypoxia, coronary flow initially increased to 189.5 +/- 17.8% of the control, and at the same time release of all PGs, except for TXB2, increased significantly (6-keto PGF1 alpha: from 3.57 +/- 0.98 to 5.54 +/- 1.25 pmol/min.g, D2: from 1.47 +/- 0.26 to 2.22 +/- 0.26 pmol/min.g, E2: from 0.27 +/- 0.08 to 0.96 +/- 0.21 pmol/min.g, F2 alpha: from 0.23 +/- 0.09 to 0.48 +/- 0.13 pmol/min.g, TXB2: from 0.61 +/- 0.10 to 0.58 +/- 0.15 pmol/min.g). During the later phase (10-20 min) of hypoxia, coronary flow decreased without concomitant decrease in the release of PGs. The administration of indomethacin (10 microM) and aspirin (1 mM) did not affect the normoxic coronary flow. However, during the early phase of hypoxia, they significantly suppressed the increase in coronary flow. Administration of arachidonic acid (1 mg/l) increased PG release 6.4-12.5-fold and increased coronary flow to 176.1 +/- 6.5% of the control level. In the presence of arachidonic acid, there was a good correlation between the coronary flow and the amount of released vasodilative PGs (PGE2 and 6-keto PGF1 alpha), suggesting the contribution of these PGs to coronary vasoregulation. On the other hand, when hearts were made hypoxic in the presence of arachidonic acid, percentage increase in PG release was much reduced, and similarly, coronary flow was not elevated. These results indicate that the increase in coronary flow during the early phase of hypoxia is mediated, at least in part, by the increased release of vasodilative PGs.
J Mol Cell Cardiol 1991 Aug
PMID:Hypoxia-induced change in prostanoids production and coronary flow in isolated rat heart. 194 92


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