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

1. The prostaglandin precursor arachidonic acid (C20:4) increases plasma renin activity in the rabbit and rat when it is infused into the renal arteries. 2. The increase in plasma renin activity after C20:4 in rats is not changed by volume expansion. 3. The inhibitor of prostaglandin synthesis indomethacin decreases plasma renin activity in the rabbit. 4. The increase plasma in renin activity after total renal ischaemia is abolished by pretreatment with indomethacin. 5. C20:4 increases dose- and time-dependent renin release from slices of rabbit kidney cortex. 6. Indomethacin or 5,8,11,14-eicosatetraynoic acid pretreatment in vivo, and addition to the incubation medium, reduces basal as well as C20:4-stimulated renin release in vitro. 7. The stimulating effect of C20:4 on renin release is assumed to be caused directly by formation of prostaglandin endoperoxides in the kidney cortex and not by prostaglandins since in vitro a natural prostaglandin endoperoxide (PGG2) and two stable synthetic prostaglandin endoperoxide analogues (EPA I and EPA II) do increase the release of renin, but PGE2 has no effect and PGF2alpha inhibits renin release.
Clin Sci Mol Med Suppl 1976 Dec
PMID:Effects of stimulation and inhibition of the renal prostaglandin synthetase system on renin release in vivo and in vitro. 82 72

The present study examines the time dependent effects of n-6 and n-3 polyunsaturated fatty acids on liver microsomal lipid metabolism in FVB mice fed a diet supplemented with a mixture of free fatty acids (mainly 18:3n-6 and 20:5n-3) at 25 mg/g diet. Significant changes in the fatty acid composition of total liver and microsomal lipids were observed after 7 days on the diets. Thereafter, some animals remained on the same diet while others were fed a diet supplemented with hydrogenated coconut oil (HCO). With the exception of 20:5n-3 which showed a slower recovery, establishment of the HCO pattern was rapid indicating that the diet-induced changes could be easily reversed. The unsaturation index, the cholesterol/phospholipid ratio and the microviscosity of the microsomal membranes were not affected by these dietary manipulations. Unsaturated fatty acid supplementation reduced the activity of delta 9 desaturase by 50%. Feeding the HCO diet to mice previously fed the EPA/GLA diet led to a progressive increase in delta 9 desaturase activity, reaching 80% of the day zero values after 14 days. The monoene content of hepatic total lipids reflected, in most cases, the changes in enzyme activity. This study shows that a low dose of a n-3 and n-6 free fatty acid mixture increases the quantities of members of the n-3 family, without loss of n-6 fatty acids in microsomal membranes and modifies the activity of delta 9 desaturase without altering the microsome physicochemical parameters.
Mol Cell Biochem 1992 Dec 16
PMID:Effect of n-3 and n-6 fatty acids on hepatic microsomal lipid metabolism: a time course study. 129 10

The Toxic Substances Control Act (TSCA) provides the U.S. Environmental Protection Agency, Office of Toxic Substances (EPA, OTS) with the authority to regulate chemical use by requiring testing and use restrictions as appropriate to protect human health. Regulation on the basis of heritable mutation induction is specifically mentioned in the Test Rule section of the law and has also been pursued for new chemical substances. A tiered scheme of mutagenicity testing has been employed and recently revised to assess mutagenicity hazard. In vivo assay systems play key roles at all three levels in the scheme, beginning with the first level of determining intrinsic mutagenicity hazard. Once intrinsic mutagenicity has been identified, the revised scheme requires an assay or assays to assess chemical interaction with gonadal DNA. Finally, the scheme contains tests that permit risk assessment for a chemical. The recently-revised Office of Pesticide Programs (OPP) mutagenicity testing requirements closely parallel those of OTS.
Environ Mol Mutagen 1991
PMID:EPA use of in vivo germ cell mutagenicity data. 174 93

The late polyadenylation signal of simian virus 40 functions with greater efficiency than the early polyadenylation signal, in turn affecting steady-state mRNA levels. Two chloramphenicol acetyltransferase (CAT) transient expression vectors, pL-EPA and pL-LPA, that differ only in their polyadenylation signals were constructed by using the early and late polyadenylation signals, respectively. In transfections of Cos, CV-1P, or HeLa cells and subsequent Northern blot analysis of CAT-specific RNA, approximately five times more steady-state CAT mRNA was produced in transfections with pL-LPA than with pL-EPA. The basis for this difference was not related to the specific promoter used or to RNA stability. Overall, the difference in steady-state mRNA levels derived from the two plasmids appeared to be attributable to intrinsic properties of the two polyadenylation signals, resulting in distinctly different cleavage and polyadenylation efficiencies. Additionally, we found that the utilization of the late polyadenylation site was dramatically reduced by deletion of sequences between 48 and 29 nucleotides 5' of the AAUAAA hexanucleotide. This reduction of mRNA levels was shown not to be caused by altered stability of mutant precursor RNAs or mRNAs, suggesting that these upstream sequences constitute an element of the late polyadenylation signal and may cause, at least to some extent, the greater efficiency of utilization of the late polyadenylation site.
Mol Cell Biol 1989 Oct
PMID:Efficiency of utilization of the simian virus 40 late polyadenylation site: effects of upstream sequences. 257 28

The former U.S. EPA OPPT tiered test scheme for heritable gene mutations included the Drosophila sex-linked recessive lethal (SLRL) test in which positive results triggered the mouse specific locus (MSL) test. However, review of available literature indicated that the evaluation of mutations in the germ cells of this insect is not a good predictor of the risk of heritable gene mutations in mammals. The database contained 29 compounds for which there were conclusive MSL test results in either spermatogonial and/or postspermatogonial cells. Results in the SLRL test were available for 27 of those compounds. Of the 24 SLRL-positive chemicals, only 13 (54%) induced heritable mutations in mice; the three SLRL-negative compounds were nonmutagenic in mouse germ cells. The overall concordance between the two tests was 59%. In contrast, results of unscheduled DNA synthesis (UDS: 18 chemicals) and alkaline elution (AE: 14 chemicals) assays in rodent testicular cells following in vivo exposure correlated well with results in the MSL test (83% and 86%, respectively). MSL test results in spermatogonia and postspermatogonia were also compared separately to the SLRL, UDS, and AE assays. The concordances for the two cell types in the SLRL relative to the MSL test were 36% and 79%, respectively, indicating that the SLRL test is extremely poor in predicting heritable gene mutations in mammalian spermatogonia. Concordances for UDS and AE assays relative to MSL test results in spermatogonia (53% and 54%, respectively) and postspermatogonia (91% and 100%, respectively) were greater. Based on these analyses, the U.S. EPA OPPT has revised its tiered test scheme using assays for interaction with gonadal DNA (e.g., UDS and AE) in place of the SLRL test.
Environ Mol Mutagen 1994
PMID:Assessing the risk of heritable gene mutation in mammals: drosophila sex-linked recessive lethal test and tests measuring DNA damage and repair in mammalian germ cells. 812 81

The specific effect of docosahexaenoic (DHA; C22:6 n-3), as compared to eicosapentaenoic acid (EPA; C20:5 n-3), on adrenoceptor function was investigated in cultured rat myocardial cells. The cardiomyocytes were grown for 24 h in a conventional seric medium, and then incubated for 96 h in a medium enriched with either DHA or EPA. After this treatment, the phospholipids of the DHA-treated cells contained approximately 20% of the total fatty acids as C22:6 n-3, and those of EPA-treated cells displayed a high content in C20:5 n-3 and its elongation product C22:5 n-3 (30% of total fatty acids). Additionally, the n-3/n-6 polyunsaturated fatty acid ratio was the same in the two groups of cells. These modifications were roughly similar in all the phospholipid classes. The contractions were monitored photometrically and no significant difference in basal frequency and contraction parameters could be detected. The stimulation of the beta-adrenergic receptors (isoproterenol 10(-7) M) resulted in a positive chronotropic effect, which was significantly higher in the DHA-rich cells. Conversely, the higher DHA content in the phospholipids appeared to induce a decrease in the affinity of the beta-receptors for the ligand (dihydroalprenolol) without alteration of the number of beta-receptor binding sites and provoked a significant decrease in isoproterenol-stimulated cAMP production (-19%). To investigate further these controversial data, the cardiomyocytes were treated with dibutyryl-cAMP, which elicited a positive chronotropic response significantly higher in the DHA-rich cells. The alpha-adrenergic stimulation by phenylephrine (3 x 10(-6) M) increased the spontaneous rate, but in a similar manner in the DHA- and EPA-enriched cells. Similarly, neither the alpha-adrenergic receptor binding characteristics nor the production of phosphoinositides was modulated by the membrane DNA content, although the phosphatidylinositol PUFAs were significantly altered. In conclusion, increasing the DHA content in membrane phospholipids did not affect the alpha-adrenergic system, but exerted a specific positive influence on the beta-adrenergic transduction mechanism, essentially through an increase of cAMP efficiency.
J Mol Cell Cardiol 1995 Nov
PMID:Effect of docosahexaenoic acid and eicosapentaenoic acid in the phospholipids of rat heart muscle cells on adrenoceptor responsiveness and mechanism. 859 1

There is evidence that dietary polyunsaturated fatty acids (PUFA) may protect against cardiovascular diseases, but the involvement of the cardiac muscle cell in this beneficial action remain largely unknown. The present study compared the respective influence of n-3 and n-6 PUFA on the function of cultured neonatal rat cardiomyocytes (CM). Cells were grown for 4 days in media enriched either n-3 (eicosapentaenoic acid, EPA and docosahexaenoic acid, DHA) or n-6 (arachidonic acid, AA) PUFA. The PUFA n-6/n-3 ratio in the phospholipids was close to 1 and 20 in the n-3 and n-6 cells, respectively. The transmembrane potentials were recorded using microelectrodes and the contractions were monitored with a photoelectric device. In physiological conditions, the increase of n-6 PUFA level in the phospholipids resulted in a significant decrease in the maximal rate of initial depolarization (-16%). In opposition, the action potential amplitude and duration were not altered, and the cell contraction outline was not affected. Ischemia was simulated in vitro using a substrate-free, hypoxia-reoxygenation procedure in a specially designed gas-flow chamber. The progressive loss of electrical activity induced by the substrate-free, hypoxic treatment was affected by the n-6/n-3 ratio, since the n-6 rich CM displayed a slower depression of the AP amplitude and duration parameters. Conversely, the recovery of the resting potential (MDP) during reoxygenation was faster in n-3 CM, whereas the recovery of the contraction parameters was unaffected by the fatty acid composition of the cells. These results suggested that, in physiological conditions, the modification of long chain PUFA balance in the phospholipids of cardiac muscle cells may modulate the initial AP upstroke, which is governed by sodium channels. Moreover, the presence of n-3 PUFA appeared to accelerate the electrical depression during substrate-free hypoxia but in turn to allow a faster recovery upon reoxygenation.
Mol Cell Biochem 1997 Oct
PMID:Influence of phospholipid long chain polyunsaturated fatty acid composition on neonatal rat cardiomyocyte function in physiological conditions and during glucose-free hypoxia-reoxygenation. 935 58

The mechanism of the hypolipidemic effect of n-3 fatty acids was studied using isolated rat hepatocytes maintained in culture. EPA and DHA caused a significant reduction in the incorporation of 3[H]-leucine into apoB associated with the VLDL produced by hepatocytes in culture when compared to that in presence of palmitic acid. Presence of indomethacin, an inhibitor of cyclo-oxygenase reversed the effect of EPA on VLDL synthesis while diethyl carbamazine an inhibitor of lipoxygenase did not show any effect suggesting that the effect of EPA may be mediated through prostaglandins. This was further tested by invivo experiments where animals were fed fish oil containing diet with and without aspirin, which inhibits formation of prostaglandins. The incorporation of 3[H]-leucine into apo B and 14[C]-acetate into cholesterol of VLDL produced by hepatocytes from aspirin treated animals were significantly high. The reversal of the effect of n-3 fatty acids by agents which inhibit the formation of prostaglandin suggests that the n-3 fatty acids may exert their effect on VLDL production by liver cells through prostaglandins.
Biochem Mol Biol Int 1997 Dec
PMID:Effect of n-3 fatty acids on VLDL production by hepatocytes is mediated through prostaglandins. 941 16

Fatty acid composition in the liver of four ringed-seal (Phoca hispida ssp.) populations, from ocean (Spitsbergen), brackish water (the Baltic Sea) and freshwater (Lake Saimaa and Lake Ladoga) were determined by gas liquid chromatography. The fatty acid compositions in liver were compared with those of the blubber of the seals, which largely reflect the fatty acid supply from marine or freshwater fish. When the ratios of 20:4n-6/20:5n-3 (arachidonic acid/eicosapentaenoic acid, AA/EPA, from 0.06 to 0.55) and n-6 PUFA/n-3 PUFA (n-6/n-3, from 0.09 to 0.35) increased from the marine to freshwater blubber, the corresponding increase in these ratios in the total lipids of the liver was 10-fold or more (AA/EPA: from 1.2 to 13.5 and n-6/n-3: from 0.9 to 3.2). Thus, when available in the diet, AA is preferentially incorporated into the lipids of pinniped liver.
Comp Biochem Physiol B Biochem Mol Biol 1998 Jun
PMID:Composition of polyunsaturated fatty acids in the liver of freshwater and marine ringed seals (Phoca hispida ssp.) differs largely due to the diet of the seals. 978 92

We explored the uses of fish oil (active EPA-30) as a source of eicosapentaenate (EPA; 20:5 n-3), to young and old rats. We treated three subgroups of rats each comprising 20 young or old rats, respectively. The first group was kept on the basal ration (lab-pellet) as control diet, the second group was fed semi-purified diets contained 5% pig-fat (n-3 fatty acids deficient diet). The third group was fed a modified diet in which 50% of pig-fat was replaced by active EPA-30. Livers of young rats fed pig-fat had a drastic decrease in the amount of phosphatidylethanolamine (PE) and omega-3 polyunsaturated fatty acids (EPA, 20:5 n-3 and docosahexaenoic, DHA, 22:6 n-3) and compensatory increase of phosphatidylcholine, saturated fatty acids and n-6 polyunsaturated fatty acids in the liver phospholipids. In contrast, the liver of young rats fed active EPA-30 had large amounts of PE and concomitant enrichment in polyunsaturated fatty acids. The liver of old rats, fed on active EPA-30 supplemented diet had lower amounts of PE and there were no significant changes in the phospholipid fatty acid composition.
Comp Biochem Physiol A Mol Integr Physiol 1999 Mar
PMID:Effect of dietary fish oil (active EPA-30) on liver phospholipids in young and aged rats. 1035 59


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