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A A Spector

Publications and source records attributed to A A Spector.

At least 37 records · Page 2Linked to original sources
PubMed2000

Role of plant-derived omega-3 fatty acids in human nutrition.

An international workshop on the role of plant-derived omega-3 fatty acids in human nutrition took place in Milan on February 9, 2000. The meeting was sponsored by the Nutrition Foundation of Italy and was organized by its Scientific Director, Dr. Andrea Poli. It was attended by experts in polyunsaturated fatty acids and human lipid nutrition. This is the first meeting devoted to the health aspects of alpha-linolenic acid, the omega-3 fatty acid contained in plant-derived edible products, as distinct from the more widely studied long-chain omega-3 products typically present in fish and fish-derived products. This report, which is based on updated scientific evidence presented and discussed at the workshop, was prepared by the international expert panel.

Animals↗
PubMed2000

Enhanced H(2)O(2)-induced cytotoxicity in "epithelioid" smooth muscle cells: implications for neointimal regression.

Vascular smooth muscle cells (SMCs) are phenotypically diverse. Although most medial SMCs can be classified as "fusiform," others are of the "epithelioid" phenotype. Proliferation and apoptosis of epithelioid SMCs may contribute importantly to neointimal formation and regression, respectively. Because reactive oxygen species (ROS) are increased in vascular injury and can induce apoptosis of SMCs, we compared the effects of ROS on epithelioid and fusiform SMCs. Epithelioid and fusiform SMC lines were clonally isolated from rat aortic media and studied under similar conditions and passage numbers. H(2)O(2) produced dose- and time-dependent cytotoxicity that was enhanced in epithelioid compared with fusiform cells. After 24-hour exposure to 50 micromol/L H(2)O(2), epithelioid cell numbers were reduced by 34+/-5% versus a 3+/-5% (P<0.05) reduction in fusiform cell numbers. Similar results were obtained whether H(2)O(2) was administered to growth-arrested or growing cells or when epithelioid and fusiform cells were exposed to extracellular O(2)(.-). To investigate whether apoptosis contributed to enhanced ROS-induced cytotoxicity in epithelioid SMCs, terminal deoxyribonucleotidyl transferase (TDT)-mediated dUTP-digoxigenin nick-end labeling (TUNEL) staining was performed. The incidence of TUNEL positivity was 5-fold increased in epithelioid versus fusiform SMCs after treatment with 50 micromol/L H(2)O(2) (19+/-1% epithelioid versus 5+/-1% fusiform, P<0.05). Enhanced H(2)O(2)-induced apoptosis in epithelioid SMCs was confirmed by DNA laddering. Furthermore, when balloon-injured aortas were exposed to H(2)O(2) ex vivo, enhanced apoptosis was observed in neointimal compared with medial SMCs. These results suggest that epithelioid SMCs exhibit enhanced sensitivity to ROS-induced apoptosis, which may play an important role in neointimal regression.

Animals↗
PubMed2000

Conversion of epoxyeicosatrienoic acids (EETs) to chain-shortened epoxy fatty acids by human skin fibroblasts.

Epoxyeicosatrienoic acids (EETs), the eicosanoid biomediators synthesized from arachidonic acid by cytochrome P450 epoxygenases, are inactivated in many tissues by conversion to dihydroxyeicosatrienoic acids (DHETs). However, we find that human skin fibroblasts convert EETs mostly to chain-shortened epoxy-fatty acids and produce only small amounts of DHETs. Comparative studies with [5,6,8,9,11,12,14,15-(3)H]11,12-EET ([(3)H]11,12-EET) and [1-(14)C]11,12-EET demonstrated that chain-shortened metabolites are formed by removal of carbons from the carboxyl end of the EET. These metabolites accumulated primarily in the medium, but small amounts also were incorporated into the cell lipids. The most abundant 11, 12-EET product was 7,8-epoxyhexadecadienoic acid (7,8-epoxy-16:2), and two of the others that were identified are 9, 10-epoxyoctadecadienoic acid (9,10-epoxy-18:2) and 5, 6-epoxytetradecaenoic acid (5,6-epoxy-14:1). The main epoxy-fatty acid produced from 14,15-EET was 10,11-epoxyhexadecadienoic acid (10, 11-epoxy-16:2). [(3)H]8,9-EET was converted to a single metabolite with the chromatographic properties of a 16-carbon epoxy-fatty acid, but we were not able to identify this compound. Large amounts of the chain-shortened 11,12-EET metabolites were produced by long-chain acyl CoA dehydrogenase-deficient fibroblasts but not by Zellweger syndrome and acyl CoA oxidase-deficient fibroblasts. We conclude that the chain-shortened epoxy-fatty acids are produced primarily by peroxisomal beta-oxidation. This may serve as an alternate mechanism for EET inactivation and removal from the tissues. However, it is possible that the epoxy-fatty acid products may have metabolic or functional effects and that the purpose of the beta-oxidation pathway is to generate these products.

Cells, Cultured↗
PubMed1999

Overexpression of human catalase inhibits proliferation and promotes apoptosis in vascular smooth muscle cells.

The role of reactive oxygen species, such as superoxide anions (O(2). (-)) and hydrogen peroxide (H(2)O(2)), in modulating vascular smooth muscle cell proliferation and viability is controversial. To investigate the role of endogenously produced H(2)O(2), rat aortic smooth muscle cells were infected with adenoviral vectors containing cDNA for human catalase (AdCat) or a control gene, beta-galactosidase (AdLacZ). Infection with AdCat resulted in dose-dependent increases in intracellular catalase protein, which was predominantly localized to peroxisomes. After infection with 100 multiplicity of infection (MOI) of AdCat, cellular catalase activity was increased by 50- to 100-fold, and intracellular H(2)O(2) concentration was reduced, as compared with control. Infection with AdCat reduced [(3)H]thymidine uptake, an index of DNA synthesis, in cells maintained in medium supplemented with 2% serum (0.37+/-0.09 disintegrations per minute per cell [AdLacZ] versus 0.22+/-0.08 disintegrations per minute per cell [AdCat], P<0.05). Five days after infection with 100 MOI of AdCat, cell numbers were reduced as compared with noninfected or AdLacZ-infected cells (157 780+/-8413 [AdCat], P<0.05 versus 233 700+/-3032 [noninfected] or 222 410+/-5332 [AdLacZ]). Furthermore, the number of apoptotic cells was increased 5-fold after infection with 100 MOI of AdCat as compared with control. Infection with AdCat resulted in induction of cyclooxygenase (COX)-2, and treatment with a COX-2 inhibitor overcame the AdCat-induced reduction in cell numbers. These findings indicate that overexpression of catalase inhibited smooth muscle proliferation while increasing the rate of apoptosis, possibly through a COX-2-dependent mechanism. Our results suggest that endogenously produced H(2)O(2) importantly modulates survival and proliferation of vascular smooth muscle cells.

Animals↗
PubMed1999

Effects of epoxyeicosatrienoic acids on the cardiac sodium channels in isolated rat ventricular myocytes.

1. Whole-cell Na+ currents (holding potential, -80 mV; test potential, -30 mV) in rat myocytes were inhibited by 8, 9-epoxyeicosatrienoic acid (8,9-EET) in a dose-dependent manner with 22+/-4% inhibition at 0.5 microM, 48+/-5% at 1 microM, and 73+/-5% at 5 microM (mean +/- S.E.M., n = 10, P<0.05 for each dose vs. control). Similar results were obtained with 5,6-, 11,12-, and 14,15-EETs, while 8,9-dihydroxyeicosatrienoic acid (DHET) was 3-fold less potent and arachidonic acid was 10- to 20-fold less potent. 2. 8,9-EET produced a dose-dependent, hyperpolarized shift in the steady-state membrane potential at half-maximum inactivation (V ), without changing the slope factor. 8,9-EET had no effect on the steady-state activation of Na+ currents. 3. Inhibition of Na+ currents by 8,9-EET was use dependent, and channel recovery was slowed. The effects of 8,9-EET were greater at depolarized potentials. 4. Single channel recordings showed 8,9-EET did not change the conductance or the number of active Na+ channels, but markedly decreased the probability of Na+ channel opening. These results were associated with a decrease in the channel open time and an increase in the channel closed times. 5. Incubation of cultured cardiac myocytes with 1 microM [3H]8,9-EET showed that 25% of the radioactivity was taken up by the cells over a 2 h period, and most of the uptake was incorporated into phospholipids, principally phosphatidylcholine. Analysis of the medium after a 2 h incubation indicated that 86% of the radioactivity remained as [3H]8,9-EET while 13% was converted into [3H]8,9-DHET. After a 30 min incubation, 1-2% of the [3H]8,9-EET uptake by cells remained as unesterified EET. 6. These results demonstrate that cardiac cells have a high capacity to take up and metabolize 8,9-EET. 8,9-EET is a potent use- and voltage-dependent inhibitor of the cardiac Na+ channels through modulation of the channel gating behaviour.

8,11,14-Eicosatrienoic Acid↗
PubMed1999

Mechanical and electromotile characteristics of auditory outer hair cells.

The passive and active properties of the cochlear outer hair cell are studied. The outer hair cell is currently considered the major candidate for the active component of mammalian hearing. Understanding of its properties may explain the amplification and sharp frequency selectivity of the ear. To analyse the cell behaviour, a model of a nonlinear anisotropic electro-elastic shell is used. Using the data from three independent experiments, where the mechanical strains of the cell are measured, estimates of the cell wall in-plane Young's moduli and Poisson's ratios are given, as well as estimates of three modes of bending stiffness. Based on these estimates and data from the microchamber experiment, where the cell is under the action of transmembrane potential changes, the characteristics of the outer hair cell active behaviour are found. These characteristics include the coefficients of the active force production per unit of the transmembrane potential change and limiting parameters of the electromotile response for extreme hyperpolarisation and depolarisation of the cell. The obtained estimates provide important information for the modelling of organ-level cochlear mechanics.

Biomechanical Phenomena↗
PubMed1999

Essentiality of fatty acids.

All fatty acids have important functions, but the term "essential" is applied only to those polyunsaturated fatty acids (PUFA) that are necessary for good health and cannot be completely synthesized in the body. The need for arachidonic acid, which is utilized for eicosanoid synthesis and is a constituent of membrane phospholipids involved in signal transduction, is the main reason why the n-6 class of PUFA are essential. Physiological data indicate that n-3 PUFA also are essential. Although eicosapentaenoic acid also is a substrate for eicosanoid synthesis, docosahexaenoic acid (DHA) is more likely to be the essential n-3 constituent because it is necessary for optimal visual acuity and neural development. DHA is present in large amounts in the ethanolamine and serine phospholipids, suggesting that its function involves membrane structure. Because the metabolism of n-6 PUFA is geared primarily to produce arachidonic acid, only small amounts of 22-carbon n-6 PUFA are ordinarily formed. Thus, the essentiality of n-3 PUFA may be due to their ability to supply enough 22-carbon PUFA for optimal membrane function rather than to a unique biochemical property of DHA.

Animals↗
PubMed1999

Nonlinear active force generation by cochlear outer hair cell.

We analyze the nonlinear behavior of the longitudinal and circumferential components of the active force generated by the outer hair cell wall in response to changes of its transmembrane potential. We treat the material of the wall as electroelastic, linear orthotropic in terms of strains and as nonlinear in terms of the transmembrane potential. To describe the nonlinear behavior of the active force versus the transmembrane potential, we use two (Boltzmann and simple exponential) types of approximation. We estimate free parameters of these approximations by combining the previously reported passive stiffnesses with the active strains measured in the microchamber experiment. We analyze the sensitivity of the estimated parameters corresponding to changes of the cell axial stiffness, a characteristic independently measured by several groups. We also study the effect of combining the active strains measured in the microchamber experiment with those measured in the whole cell recording experiment. We show agreement between our prediction of the active force and measurements in the whole cochlea and in isolated cells.

Cell Movement↗
PubMed1999

Epoxide hydrolases regulate epoxyeicosatrienoic acid incorporation into coronary endothelial phospholipids.

Cytochrome P-450-derived epoxyeicosatrienoic acids (EETs) are avidly incorporated into and released from endothelial phospholipids, a process that results in potentiation of endothelium-dependent relaxation. EETs are also rapidly converted by epoxide hydrolases to dihydroxyeicosatrienoic acid (DHETs), which are incorporated into phospholipids to a lesser extent than EETs. We hypothesized that epoxide hydrolases functionally regulate EET incorporation into endothelial phospholipids. Porcine coronary artery endothelial cells were treated with an epoxide hydrolase inhibitor, 4-phenylchalcone oxide (4-PCO, 20 micromol/l), before being incubated with (3)H-labeled 14,15-EET (14,15-[(3)H]EET). 4-PCO blocked conversion of 14,15-[(3)H]EET to 14,15-[(3)H]DHET and doubled the amount of radiolabeled products incorporated into cell lipids, with >80% contained in phospholipids. Moreover, pretreatment with 4-PCO before incubation with 14,15-[(3)H]EET enhanced A-23187-induced release of radiolabeled products into the medium. In contrast, 4-PCO did not alter uptake, distribution, or release of [(3)H]arachidonic acid. In porcine coronary arteries, 4-PCO augmented 14,15-EET-induced potentiation of endothelium-dependent relaxation to bradykinin. These data suggest that epoxide hydrolases may play a role in regulating EET incorporation into phospholipids, thereby modulating endothelial function in the coronary vasculature.

8,11,14-Eicosatrienoic Acid↗
PubMed1999

Epoxyeicosatrienoic acids increase intracellular calcium concentration in vascular smooth muscle cells.

Epoxyeicosatrienoic acids (EETs) are cytochrome P450-derived metabolites of arachidonic acid. They are potent endogenous vasodilator compounds produced by vascular cells, and EET-induced vasodilation has been attributed to activation of vascular smooth muscle cell (SMC) K(+) channels. However, in some cells, EETs activate Ca(2+) channels, resulting in Ca(2+) influx and increased intracellular Ca(2+) concentration ([Ca(2+)](i)). We investigated whether EETs also can activate Ca(2+) channels in vascular SMC and whether the resultant Ca(2+) influx can influence vascular tone. The 4 EET regioisomers (1 micromol/L) increased porcine aortic SMC [Ca(2+)](i) by 52% to 81%, whereas arachidonic acid, dihydroxyeicosatrienoic acids, and 15-hydroxyeicosatetraenoic acid (1 micromol/L) produced little effect. The increases in [Ca(2+)](i) produced by 14,15-EET were abolished by removal of extracellular Ca(2+) and by pretreatment with verapamil (10 micromol/L), an inhibitor of voltage-dependent (L-type) Ca(2+) channels. 14,15-EET did not alter Ca(2+) signaling induced by norepinephrine and thapsigargin. When administered to porcine coronary artery rings precontracted with a thromboxane mimetic, 14,15-EET produced relaxation. However, when administered to rings precontracted with acetylcholine or KCl, 14,15-EET produced additional contractions. In rings exposed to 10 mmol/L KCl, a concentration that did not affect resting ring tension, 14,15-EET produced small contractions that were abolished by EGTA (3 mmol/L) or verapamil (10 micromol/L). These observations indicate that 14,15-EET enhances [Ca(2+)](i) influx in vascular SMC through voltage-dependent Ca(2+) channels. This 14,15-EET-induced increase in [Ca(i)(2+)] can produce vasoconstriction and therefore may act to modulate EET-induced vasorelaxation.

8,11,14-Eicosatrienoic Acid↗
PubMed1999

13-(S)-hydroxyoctadecadienoic acid (13-HODE) incorporation and conversion to novel products by endothelial cells.

13(S)-Hydroxy-[12,13-3H]octadecadienoic acid (13-HODE), a linoleic acid oxidation product that has vasoactive properties, was rapidly taken up by bovine aortic endothelial cells. Most of the 13-HODE was incorporated into phosphatidylcholine, and 80% was present in the sn -2 position. The amount of 13-HODE retained in the cells gradually decreased, and radiolabeled metabolites with shorter reverse-phase high-performance liquid chromatography retention times (RT) than 13-HODE accumulated in the extracellular fluid. The three major metabolites were identified by gas chromatography combined with mass spectrometry as 11-hydroxyhexadecadienoic acid (11-OH-16:2), 9-hydroxytetradecadienoic acid (9-OH-14:2), and 7-hydroxydodecadienoic acid (7-OH-12:2). Most of the radioactivity contained in the cell lipids remained as 13-HODE. However, some 11-OH-16:2 and several unidentified products with longer RT than 13-HODE were detected in the cell lipids. Normal human skin fibroblasts also converted 13-HODE to the three major chain-shortened metabolites, but Zellweger syndrome fibroblasts produced only a very small amount of 11-OH-16:2. Therefore, the chain-shortened products probably are formed primarily by peroxisomal beta-oxidation. These findings suggest that peroxisomal beta-oxidation may constitute a mechanism for the inactivation and removal of 13-HODE from the vascular wall. Because this is a gradual process, some 13-HODE that is initially incorporated remains in endothelial phospholipids, especially phosphatidylcholine. This may be the cause of some of the functional perturbations produced by 13-HODE in the vascular wall.

Animals↗
PubMed1998

Overexpression of human superoxide dismutase inhibits oxidation of low-density lipoprotein by endothelial cells.

Oxidation of LDL in the subendothelial space has been proposed to play a key role in atherosclerosis. Endothelial cells produce superoxide anions (O2.-) and oxidize LDL in vitro; however, the role of O2.- in endothelial cell-induced LDL oxidation is unclear. Incubation of human LDL (200 microg/mL) with bovine aortic endothelial cells (BAECs) for 18 hours resulted in a 4-fold increase in LDL oxidation compared with cell-free incubation (22.5+/-1.1 versus 6.3+/-0.2 [mean+/-SEM] nmol malondialdehyde/mg LDL protein, respectively; P<0.05). Under similar conditions, incubation of LDL with porcine aortic endothelial cells resulted in a 5-fold increase in LDL oxidation. Inclusion of exogenous copper/zinc superoxide dismutase (Cu/ZnSOD, 100 microg/mL) in the medium reduced BAEC-induced LDL oxidation by 79%. To determine whether the intracellular SOD content can have a similar protective effect, BAECs were infected with adenoviral vectors containing cDNA for human Cu/ZnSOD (AdCu/ZnSOD) or manganese SOD (AdMnSOD). Adenoviral infection increased the content and activity of either Cu/ZnSOD or MnSOD in the cells and reduced cellular O2.- release by two thirds. When cells infected with AdCu/ZnSOD or AdMnSOD were incubated with LDL, formation of malondialdehyde was decreased by 77% and 32%, respectively. Two other indices of LDL oxidation, formation of conjugated dienes and increased LDL electrophoretic mobility, were similarly reduced by SOD transduction. These data suggest that production of O2.- contributes to endothelial cell-induced oxidation of LDL in vitro. Furthermore, adenovirus-mediated transfer of cDNA for human SOD, particularly Cu/ZnSOD, effectively reduces oxidation of LDL by endothelial cells.

Adenoviridae↗
PubMed1998

Gamma-linolenic acid (GLA) is cytotoxic to 36B10 malignant rat astrocytoma cells but not to 'normal' rat astrocytes.

This study compares the effect of gamma-linolenic acid (GLA) and its precursor linoleic acid (LA) on survival of 36B10 malignant rat astrocytoma cells and 'normal' rat astrocytes. GLA was cytotoxic to 36B10 cells but not to astrocytes. By contrast, LA supplementation did not affect the survival of either cell types. There were minor differences in the uptake, distribution and use of radiolabelled GLA and LA by the 36B10 cells and astrocytes. GLA and LA supplementation increased the total polyunsaturated fatty acid (PUFA) content of the cells indicating increased oxidative potential. However, elevated levels of 8-isoprostane, an indicator of increased oxidative stress, were only observed in the GLA supplemented 36B10 cells. Addition of the antioxidant trolox to GLA-enriched 36B10 cells blocked the cytotoxic effect. Further, GLA enhanced the radiation sensitivity of the astrocytoma cells but not the astrocytes; trolox blocked the GLA-mediated increase in astrocytoma cell radiosensitivity. LA did not affect the radiation response of either cell type. While cyclo-oxygenase inhibitors did not affect GLA cytotoxicity, they blocked the enhanced radiation response of GLA-supplemented cells. The lipoxygenase inhibitor NDGA did not affect the toxicity produced by GLA. Thus, GLA is toxic to the neoplastic astrocytoma cells but not to normal astrocytes.

Animals↗
PubMed1998

Analysis of the micropipet experiment with the anisotropic outer hair cell wall.

The in-plane and bending stiffnesses of the outer hair cell wall are characteristics crucial to the understanding of force and energy transmission between cochlear elements. A mathematical interpretation is given of the micropipet experiment directed at determining the outer hair cell wall stiffness. On the basis of the microstructural observation of the wall showing that it comprises protein networks with different elastic properties, the model of an orthotropic cylindrical shell is used. The boundary-value problem is analyzed corresponding to the stress-strain of the wall (shell) caused by the action of the micropipet. The solution is given in terms of Fourier series with respect to the circumferential coordinate. An asymptotic analysis of the solution is developed and an approximate formula for the length of the tongue aspirated within the pipet is derived. This leads to an analytical expression for the stiffness parameter measured in the micropipet experiment in terms of Young's moduli and Poisson's ratios of the wall. This expression is an important part of the estimation of the elastic constants of the wall.

Anisotropy↗
PubMed1998

Estimation of elastic moduli and bending stiffness of the anisotropic outer hair cell wall.

The outer hair cell makes both passive and active contributions to basilar membrane mechanics. The outer hair cell mechanics is strongly coupled to the elastic properties of the cell lateral wall. The lateral wall experiences both in-plane deformations and bending under physiological and experimental conditions. To characterize the outer hair cell wall, the model of an orthotropic cylindrical shell is used. The elastic constants of the wall are estimated by solving a set of three equations based on the analyses of three independent experiments. The first equation is derived from a new interpretation of the micropipet experiment; the other two are obtained from the axial loading and the osmotic challenge experiments. The two Young's moduli corresponding to the longitudinal and circumferential directions and two Poisson's ratios are estimated. The longitudinal, circumferential, and mixed modes of the bending stiffness are also estimated. The sensitivity of the derived constants to the variation of the cell axial stiffness, which has been measured by several independent groups, is examined. The new estimates are also compared with results obtained by using the assumption of the wall isotropy.

Anisotropy↗
PubMed1998

14,15-Epoxyeicosatrienoic acid inhibits prostaglandin E2 production in vascular smooth muscle cells.

14,15-Epoxyeicosatrienoic acid (EET), a cytochrome P-450 epoxygenase product of arachidonic acid (AA), reduced PGE2 formation by 40-75% in porcine aortic and murine brain microvascular smooth muscle cells. The inhibition was reversed 6-10 h after removal of 14,15-EET from the medium and was regioisomeric specific; 8,9-EET produced a smaller effect, whereas 11,12- and 5,6-EET were ineffective. Although the cells converted 14,15-EET to 14, 15-dihydroxyeicosatrienoic acid (14,15-DHET), 14,15-DHET did not inhibit PGE2 formation, and the 14,15-EET-induced inhibition was potentiated by 4-phenylchalcone oxide, an epoxide hydrolase inhibitor. The inhibition occurred when substrate amounts of AA were used and was not accompanied by enhanced production of other PGs, suggesting an effect on PGH synthase; however, in murine cells, 14, 15-EET did not reduce PGH synthase mRNA or protein. Moreover, the 14, 15-EET-induced decrease in PGE2 production was overcome by increasing the concentration of AA, but not oleic acid (which is not a substrate for PGH synthase). These findings suggest that 14,15-EET competitively inhibits PGH synthase activity in vascular smooth muscle cells. The 14,15-EET-induced inhibition of PGE2 production resulted in potentiation of platelet-derived growth factor-induced smooth muscle cell proliferation, suggesting that the competitive inhibition of PGH synthase by 14,15-EET can affect growth responses in smooth muscle cells.

8,11,14-Eicosatrienoic Acid↗
PubMed1998

Conversion of eicosapentaenoic acid to chain-shortened omega-3 fatty acid metabolites by peroxisomal oxidation.

Human skin fibroblasts can convert arachidonic acid to 14- and 16-carbon polyunsaturated fatty acid products by peroxisomal beta-oxidation. The purpose of this study was to determine whether similar products are formed from eicosapentaenoic acid (EPA) and whether EPA and arachidonic acid compete for utilization by this oxidative pathway. Three radiolabeled metabolites with shorter retention times than EPA on reverse-phase high-performance liquid chromatography accumulated in the medium during incubation of fibroblasts with [5,6,8,9,11,12,14,15,17,18-3H] EPA ([3H]EPA). These metabolites, which were not formed from [1-14C]EPA and were not detected in the cells, were identified as tetradecatrienoic acid (14:3n-3), hexadecatetraenoic acid (16:4n-3), and octadecatetraenoic acid (18:4n-3). The most abundant product under all of the conditions tested was 16:4n-3. [3H]EPA was converted to 16:4n-3 and 14:3n-3 by fibroblasts deficient in mitochondrial long-chain acyl CoA dehydrogenase, but not by Zellweger syndrome or acyl CoA oxidase mutants that are deficient in peroxisomal beta-oxidation. Competition studies indicated that 16:4n-3 formation from 5 microM [3H]EPA was reduced by 60% when 10 microM arachidonic acid was added, but the conversion of [3H]arachidonic acid to its chain-shortened products was not decreased by the addition of 10 microM EPA. These findings demonstrate that as in the case of arachidonic acid, chain-shortened polyunsaturated fatty acid products accumulate when EPA undergoes peroxisomal beta-oxidation. While EPA does not reduce arachidonic acid utilization by this pathway, it is possible that some biological actions of EPA may be mediated by the formation of the corresponding EPA products, 16:4n-3 and 14:3n-3.

Arachidonic Acid↗