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

The susceptibility to ventricular arrhythmias under the conditions of cardiac ischemia and reperfusion was investigated in the Langendorff heart preparation of rats fed for eight weeks a standard chow enriched with 2% of pulverized wild garlic leaves. The isolated hearts were perfused with a modified Krebs-Henseleit solution. The incidence of ventricular fibrillation (VF) during 20 min occlusion of the descending branch of the left coronary artery (LAD) was significantly reduced in the wild garlic group as compared to untreated controls (20% vs 88%). The same holds for the size of the ischemic zone (33.6% vs 40.9% of heart weight). In the reperfusion experiments (5 min after 10 min ischemia), ventricular tachycardia (VT) occurred in 70% of the wild garlic group vs 100% in untreated controls and VF in 50% vs 90%. The time until occurrence of extrasystoles, VT or VR was prolonged. No significant alterations in cardiac fatty acid composition could be observed. Although the prostacyclin production was slightly increased in hearts of the wild garlic group, inhibition of cyclooxygenase by acetylsalicylic acid (ASA; aspirin) could not completely prevent the cardioprotective effects suggesting that the prostaglandin system does not play a decisive role in the cardioprotective action of wild garlic. Furthermore, a moderate angiotensin converting enzyme (ACE) inhibiting action of wild garlic was found in vitro as well as in vivo that could contribute to the cardioprotective and blood pressure lowering action of wild garlic. Whether a free radical scavenging activity of wild garlic is involved in its cardioprotective effects remains to be established.
Mol Cell Biochem 1993 Feb 17
PMID:Cardioprotective actions of wild garlic (allium ursinum) in ischemia and reperfusion. 845 76

A number of clinical states have been described where there are derangements or discrepancies between renin-angiotensin and aldosterone secretion. We have studied the potential effect of some cytokines or growth factors (peptide regulatory factors) on this system in vitro. Both tumor necrosis factor/cachectin and interleukin I are potent regulators acting as renin secretagogues and inhibitors of aldosterone synthesis. These actions are mediated by prostaglandin cyclooxygenase products and their actions mimic the syndrome of hyperreninemic hypoaldosteronism in critical illness. Insulin and insulin-like growth factor I are also renin secretagogues in vitro However in a diabetic model (streptozotocin rat), there is resistance to both agonists as well as enhanced feedback suppression to angiotensin. A third peptide, transforming growth factor (TGF beta) has even more complex actions, acting as a secretagogue at low doses (10(-12) M) but inhibiting renin at higher doses. TGF beta production is increased in the diabetic state so that this peptide as well as the insulin family may be involved in hyporeninemic hypoaldosteronism.
J Steroid Biochem Mol Biol 1993 Apr
PMID:Paracrine regulation of the renin-aldosterone system. 848 48

We report on prostaglandin (PG) biosynthesis in the lone star tick, Amblyomma americanum. In vitro preparations of whole female ticks and internal tissues were competent to biosynthesize four PGs: PGA2/PGB2, PGD2, PGE2, PGF2 alpha. PGA2/PGB2 was the major product under optimal conditions. PG biosynthesis by whole tick and internal tissues were sensitive to incubation conditions including, protein concentration, time, temperature, pH, and presence of a co-factor cocktail composed of reduced glutathione, hydroquinone, and hemoglobin. Under standard assay conditions, 2 mg/ml protein were incubated at pH 8.0 for 2 min at 32 degrees C. PG biosynthesis was inhibited by indomethacin, a potent cyclooxygenase inhibitor in mammalian systems. Internal tissue preparations were fractionated into cytosolic and microsomal preparations by ultracentrifugation. PG biosynthetic activity was detected in both fractions. The subcellular distribution of PG biosynthetic activity in ticks is similar to other invertebrates, but quite different from mammals, in which PG biosynthetic activity is almost exclusively localized in the microsomal fractions. PGH synthase-2 was detected in the microsomal fraction on western blot analysis. These results suggest that the lone star tick is competent to biosynthesize PGs. These compounds may contribute to the success of tick feeding ecology by attenuating the defense responses of vertebrate hosts during lengthy feeding periods.
Insect Biochem Mol Biol 1995 Oct
PMID:Prostaglandin biosynthesis and subcellular localization of prostaglandin H synthase activity in the lone star tick, Amblyomma americanum. 854 84

The effect of zinc on the repair of wounded monolayers of bovine aortic endothelial cells in a culture system was investigated. It was morphologically found that zinc promotes the appearance of the cells in the wounded area; cell number in the area was significantly increased by zinc. However, other heavy metals including copper, manganese, nickel and cobalt failed to exhibit a similar effect. The repair induced by exogenous basic fibroblast growth factor (bFGF) was potentiated by zinc but that by exogenous acidic fibroblast growth factor was unaffected by the metal. Promotion of the repair of the wounded area by zinc was completely blocked by either cycloheximide or anti-bFGF antibody. In addition, zinc-induced repair was significantly inhibited by a lipoxygenase inhibitor, nordihydroguaiaretic acid but not by a cyclooxygenase inhibitor, indomethacin. From these results, it is suggested that zinc promotes the repair process of damaged vascular endothelium through the lipoxygenase pathway that mediates the response of vascular endothelial cells to endogenous bFGF.
Res Commun Mol Pathol Pharmacol 1995 Aug
PMID:Zinc promotes the repair of wounded monolayers of cultured vascular endothelial cells. 855 73

Schistosoma mansoni has previously been reported to synthesize a wide range of eicosanoids including prostaglandins, leukotrienes and hydroxyeicosatetraenoic acids (HETEs). Our analysis of arachidonic acid metabolites synthesized by microsomal and cytosolic extracts from adult S. mansoni using thin-layer chromatography and radioimmunoassay techniques indicate the presence of a soluble, enzymatically active lipoxygenase (Lox) and the absence of any cyclooxygenase (Cox) activity. The S. mansoni Lox activity catalyzed the formation of a 15-hydroxyeicosatetraenoic acid (15-HETE)-like species. This activity was calcium-independent and inhibitable by inhibitors of mammalian and plant Lox. The conversion of linoleic acid to a 13-hydroxyoctadecadienoic acid (13-HODE)-like product by S. mansoni extracts indicates that the parasite Lox-homologue is similar to mammalian 15-Lox. Immunoblot analysis of S. mansoni extracts using antisera to different mammalian lipoxygenases detects two immunoreactive proteins with molecular weights similar to plant and mammalian lipoxygenases. In addition, polymerase chain reaction (PCR) amplification of Lox-like sequences from S. mansoni genomic DNA using degenerate primers based on conserved plant and mammalian Lox sequences, generated two PCR products which hybridized to a human 15-Lox cDNA probe. While the role of eicosanoid production in the physiology of S. mansoni is not known, eicosanoids may be essential for normal physiological processes as is the case in other invertebrates. Interestingly, 15-HETE has previously been shown to have immunosuppressive effects in mammals, and this may be related to the ability of the parasite to overcome host immune responses.
Mol Biochem Parasitol 1995 Jul
PMID:Characterization of arachidonic-acid-metabolizing enzymes in adult Schistisoma mansoni. 857 45

Gallbladder cell cultures obtained from rabbits subjected to sham or 72 h of bile duct ligation (72 h BDL, cholecystitis model) were incubated with calcium ionophore (A23187), dibutyryl cAMP (cAMP), and phorbol 12,13-diacetate (phorbol) to determine the intracellular signal transduction mechanisms responsible for increased inflamed gallbladder eicosanoid synthesis. Incubation of sham and 72 h BDL cell cultures with A23187 or phorbol significantly increased, whereas cAMP decreased, release of 6-keto-PGF1 alpha, PGE2, thromboxane B2 (measured by enzyme immunoassay) in a dose-related manner. Seventy-two-hour BDL cell cultures contained a specific 2-fold increased level of prostacyclin synthase compared to sham cell cultures which was not altered by preincubation with A23187, phorbol or cAMP. These findings suggest that increased PGI2 release in the sham and inflamed cell cultures following A23187 and phorbol stimulation was mediated in part via the inositol triphosphate pathway and protein kinase C activation and was not associated with altered cyclooxygenase or prostacyclin synthase content.
Mol Cell Endocrinol 1995 Nov 30
PMID:Regulation of eicosanoid synthesis in fibroblasts from inflamed gallbladders. 867 62

We examined the effect of reversible ischemia on the transcription of prostaglandin endoperoxide synthase (PGHS-1) and c-fos mRNA in rat cerebral cortex. The level of PGHS-1 mRNA climaxed after 30 min of ischemia whereas transcription of c-fos mRNA peaked after 60 min of postischemic reperfusion. We conclude that cerebral ischemia causes early transcription of PGHS-1, without modulation by the c-fos gene or its translated product.
Brain Res Mol Brain Res 1996 Jan
PMID:Induction of PGH synthase and c-fos mRNA during early reperfusion of ischemic rat brain. 871 74

Leukocytes can take part in an inflammatory response in the heart after myocardial infarction or cardio-thoracic surgery. To investigate the injurious mechanism of activated polymorphonuclear leukocytes (PMN), isolated rat hearts were perfused with phorbol 12-myristate 13-acetate (PMA) activated PMN (3 x 10(6)/ml) alone for 10 min, in combination with a mixture of oxygen free radical scavengers (superoxide dismutase+catalase+thiourea) or in combination with ibuprofen (IBU), a cyclooxygenase inhibitor or diethylcarbamazine (DCM), a lipoxygenase inhibitor or BW 755C, a dual inhibitor of cyclooxygenase and lipoxygenase and an oxygen free radical scavenger. After 30 min of recovery, the hearts were perfusion-fixed with glutaraldehyde for electron microscopical examination. Based on examination of 25 micrographs per heart obtained by a random sampling procedure and on morphometric methods, volume fractions (Vv) of mitochondria (mito), altered mitochondria (alt mito), myofilament, and cellular edema were measured as fractions of myocyte volume. The most important finding was that Vv(alt mito/myocyte) was 0.09 +/- 0.16 and 0.02 +/- 0.04 in the hearts receiving PMN+PMA alone and when scavengers were added, respectively, whilst no changes in mitochondrial ultrastructure was observed after addition of IBU, BW 755C or DCM. Vv(mito/myocyte) was for PMN+PMA alone: 0.33 +/- 0.04, +scavengers: 0.29 +/- 0.02 +IBU:0.29 +/- 0.02, +BW 755C: 0.23 +/- 0.03*, +DCM: 0.28 +/- 0.02 (mean +/- S.D., *P < 0.05 compared to PMN+PMA). Capillary wall volume (cap wall) as a fraction of the whole capillary was also quantified. Vv(cap wall/cap) was for PMN+PMA alone: 0.26 +/- 0.06, +scavengers: 0.22 +/- 0.03, +IBU: 0.19 +/- 0.04*, +BW755C: 0.21 +/- 0.03, +DCM: 0.15 +/- 0.04* (*P < 0.05). These results further strengthen the notion that activated PMN are intravascularly active. In addition to exerting a cardiodepressive effect the present study shows that activated PMN can induce structural changes in the heart through the combined action of oxygen free radicals and arachidonic acid metabolites.
J Mol Cell Cardiol 1996 Feb
PMID:Cardiac injury by activated leukocytes: effect of cyclooxygenase and lipoxygenase inhibition evaluated by electron microscopical morphometry. 872 63

Cultured astroglial cells secrete eicosanoids which are produced by the cyclooxygenase and lipoxygenases. These cells also transcribe the proenkephalin gene. In the present study, it was investigated whether agents which inhibit the metabolism of arachidonic acid affect the basal and stimulated expression of the gene. Tetradecanoyl phorbol acetate (TPA; 1-1000 nmol/l) increases the concentration of proenkephalin mRNA in these cells by activating protein kinase C. The enhancement in proenkephalin mRNA caused by TPA (10 nmol/l) was not affected by the cyclooxygenase inhibitor indomethacin (5 mumol/l). However, nordihydroguaiaretic acid, which blocks cyclooxygenase and lipoxygenases, potentiated the effect of TPA on proenkephalin mRNA, when used at concentrations of 0.5-50 mumol/l. Two selective inhibitors of 5-lipoxygenase, i.e. MK886 (5 mumol/l) and BAY X1005 (1 mumol/l), also enhanced the effect of TPA (10 nmol/l) without affecting the basal expression of the gene. When added to the incubation medium, leukotriene E4 (10-1000 nmol/l) diminished in a dose-dependent manner the basal and TPA-induced expression of the proenkephalin gene. It is concluded that in astroglial cells derived from cortex of new-born rats products of 5-lipoxygenase can diminish the action of protein kinase C on the proenkephalin gene.
Brain Res Mol Brain Res 1995 Oct
PMID:Evidence for the involvement of 5-lipoxygenase products in the regulation of the expression of the proenkephalin gene in cultured astroglial cells. 877 48

Bradykinin and prostaglandins are established mediators of exudative and inflammatory phases of healing. Their contribution to the fibrogenic component of healing in the heart is less certain. We therefore undertook the present study in rats with acute myocardial infarction (MI) following left coronary artery ligation. Treatment with a bradykinin B2 receptor antagonist (Hoe140, 0.5 microgram/kg/min s.c.) or a cyclooxygenase inhibitor (indomethacin, 2 mg/kg p.o.), initiated 24 h after surgery, was examined for responses in MI topography (size and area), MI and nonMI tissue fibrosis (fibrillar collagen specific picrosirius red). Early (week 1) and late (week 4) phases of fibrogenesis postMI were examined. Compared to control, we found: (1) MI size at weeks 1 and 4 was comparable in untreated and treated rats: (2) infarct area, a measure of scar thickness, was reduced (P < 0.05) at week 4 by each intervention; and (3) densitometric collagen volume fraction did not reveal a reduction in collagen accumulation at the MI site, but this was evident remote to the MI (P < 0.05) at week 4 for each agent. Thus, pharmacological interference with bradykinin-receptor binding or prostaglandin synthesis following MI is associated with reduced fibrillar collagen formation. Though the mechanism responsible for observed alteration in fibrogenesis is uncertain, anti-inflammatory and anti-proliferative properties of these agents may be responsible.
J Mol Cell Cardiol 1996 Jun
PMID:Wound healing following myocardial infarction in the rat: role for bradykinin and prostaglandins. 878 69


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