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PubMed1997

Vagal and sympathetic denervation in the development of oleic acid-induced pulmonary edema.

This study investigates the effects of autonomic denervation on extravascular lung water, pulmonary hemodynamics, the filtration coefficient of pulmonary vasculature and oxygenation in the development of pulmonary edema. Thirty seven dogs were divided into seven groups. No experimental treatment was conducted in group Nc (n = 4, sham operation) or group Nv (n = 6, bilateral vagotomy) during a 3 h observation period. In the following groups, oleic acid (0.06 ml/kg) was injected into a central vein to induce pulmonary edema: group OAc (n = 6, intact innervation); group OAv (n = 6, bilateral vagotomy); group OAa (n = 6, alpha-blockade by phentolamine); group OAs (n = 6, alpha- and beta-blockade by sympathectomy); and group OAvs (n = 3, vagosympathectomy). The results showed that in the dogs with normal lungs, bilateral vagotomy per se did not cause lung injury during 3 h of observation. However, in oleic acid pulmonary edema, vagotomy significantly deteriorated pulmonary edema by increasing pulmonary intravascular pressures; Alpha- or alpha- and beta- sympathetic inhibition deteriorated pulmonary edema by increasing pulmonary microvascular permeability. The severity of oleic acid-induced pulmonary edema was same in the dogs with vagosympathectomy as in the dogs with intact innervation. These results suggest the inhibition of vagal or sympathetic innervation will aggravate pulmonary edema in the dog.

Animals↗
PubMed1999

Thromboxane A2 fails to induce proliferation of smooth muscle cells enriched with eicosapentaenoic acid and docosahexaenoic acid.

Thromboxane A2 (TXA2) released from aggregating platelets and injured vessel wall stimulates smooth muscle cell proliferation, which may contribute to the development of vascular lesion formation after percutaneous transluminal coronary angioplasty. Polyunsaturated fatty acids (n-3) present in the fish oils have been shown to have anti-atherosclerotic effects. In view of this, we examined the effect of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), the active ingredients of fish oils on TXA2 induced smooth muscle cell proliferation. To find out the specificity of these fatty acids we used gamma-linolenic acid (n-6) and oleic acid (n-9) as controls. It was found that TXA2 failed to stimulate proliferation of smooth muscle cells preloaded with EPA or DHA but not with gamma-linolenic acid or oleic acid. Further, when smooth muscle cells were preloaded with both EPA and DHA, they acted together in preventing the TXA2 induced smooth muscle cell proliferation. These results demonstrate that one of the mechanisms by which fish oils may prevent neointima formation is by making smooth muscle cells less responsive to TXA2 induced proliferation of smooth muscle cells.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed2006

Effect of terbutaline on alveolar liquid clearance after oleic acid-induced lung injury in rats.

OBJECTIVE: To investigate whether terbutaline affects alveolar liquid clearance after oleic acid-induced lung injury in rats. METHODS: Forty healthy Wistar rats (weighing 250-280 g) were randomly divided into five groups (n=8 in each group): the normal control group (control group), oleic acid injury group (injury group), terbutaline-treated group (terbutaline group), terbutaline plus amiloride-treated group (terbutaline+amiloride group) and terbutaline plus ouabain-treated group (terbutaline+ouabain group). Acute lung injury model was induced by intravenous oleic acid (0.25 ml/kg body weight). 24 hours later, 1.5 microCi (125) I-labeled 5% albumin solution (5 ml/kg body weight) was dripped into the lungs through trachea. The alveolar liquid clearance rate, extravascular lung water content, and arterial blood gas were measured 1 hour thereafter. RESULTS: At 24 hours after infusion of oleic acid, the rats developed pulmonary edema and severe hypoxemia, with the alveolar liquid clearance rate decreased by 49.2% and the extravascular lung water content elevated by 47.9%. Compared with the rats in the injury group, terbutaline (10(-4) mol/L) significantly increased the alveolar liquid clearance rate, decreased the extravascular lung water content and improved hypoxemia. The effect of terbutaline was partly blocked by amiloride and ouabain, which were inhibitors of sodium transport. Terbutaline increased the alveolar liquid clearance rate by 63.7%, and amiloride and ouabain reduced the alveolar liquid clearance rate by 54.7% and 56.8%, respectively. CONCLUSIONS: Terbutaline can accelerate alveolar liquid clearance through increasing sodium transport to attenuate pulmonary edema, thus improving gas exchange, which may have therapeutical effect on pulmonary edema after acute lung injury.

Adrenergic beta-Agonists↗
PubMed1982

Studies on the in vivo synthesis of triacylglycerol in mouse liver.

The in vivo biosynthesis of hepatic glycerolipids was examined by studying the incorporation of [2-3H] glycerol into triacylglycerol in the mouse. The isotope was administered by rapid injection into the portal vein. The incorporation of glycerol was linear for about 1 min and maximal rates were seen in the presence of additional oleic acid. At 20 mumol of oleic acid bound to 1 mumol of bovine serum albumin, the highest level tested, glycerol incorporation was still increasing linearly, whereas a plateau was reached at 4 mumol of glycerol. The liver incorporated 200-300 nmol of [2-3H] glycerol into triacyglycerol per min when 20 mumol of albumin-bound oleic acid plus 4 mumol of glycerol were injected in a 0.2 ml volume. Studies on the uptake by the liver after intraportal injection revealed that at 0.5 min the liver retained 2 mumol of glycerol and 5 mumol of oleic acid, indicating that the uptake of substrate was not rate-limiting. The results suggest that the availability of substrate is a major factor in the regulation of triacyglycerol biosynthesis by the liver.

Animals↗
PubMed2001

Menopause-induced changes in lipid fractions and total fatty acids in plasma.

UNLABELLED: The purpose of the present work was to evaluate the changes induced by the menopause in plasma lipids and total fatty acids. METHODS: 35 post-menopausal and 25 non-postmenopausal women were included in the study. Plasma triglycerides (TG), total cholesterol (TC) and HDL-C concentrations were detemined enzymatically. Plasma fatty acids were determined by capillary gas chromatography. RESULTS: Total cholesterol was higher (p < 0.05) in the postmenopausal women (6.18 +/- 0.77 mmol/l vs. 5.21 +/- 0.85 mmol/l). No significant changes were observed, however, in TG, HDL-C or LDL-C. The study of plasma fatty acids showed the post-menopausal women to have raised levels (p < 0.05) of stearic acid (C18:0), oleic acid (C18:1), and decrease of arachidonic acid (C20:4). Also noteworthy was the significant decrease (p < 0.001) of the desaturation index D5 (3.82 +/- 1.75) in the post-menopausal women. The SHBG level was lower (p <0.001) in the post-menopausal women (55.98 +/- 20nmol/l) than in the non-menopausal women (68.36 +/- 30 nmol/l). Multivariate analysis revealed correlation between menopause and SHBG (r = -0.3904, p < 0.05), D5 (r = -0.500, p < 0.001), TC (r = 0.3137, p <0.05), stearic acid (r = 03564, p < 0.05) and oleic acid (r = 0.2954, p < 0.05). CONCLUSION: In post-menopausal women, as well as higher total cholesterol, the alterations in plasma fatty acids may constitute an important risk factor for cardiovascular diseases.

Adult↗
PubMed1988

Catalase pretreatment attenuates oleic acid-induced edema in isolated rabbit lung.

Because reactive O2 metabolites have been demonstrated to be potent mediators of vascular dysfunction and are synthesized by lung tissue, their involvement as mediators of oleic acid (OA)-induced pulmonary edema in the isolated Krebs-perfused rabbit lung was assessed. Injection of OA (0.1 ml) into the pulmonary artery after vehicle pretreatment induced marked increases in lung weight [50.4 +/- 13.9 vs. 4.2 +/- 2.0 (SE) g 45 min after OA or vehicle, respectively, P less than 0.05], an index of pulmonary edema, and airway pressure. OA also caused a significant though minimal increase in pulmonary arterial pressure. Pretreatment with catalase (1,000 U/ml), a scavenger of H2O2, significantly (P less than 0.05, Friedman's) attenuated the increases in lung weight (50.4 +/- 13.9 vs. 15.1 +/- 4.9 g), airway pressure, and pulmonary arterial pressure. In contrast to catalase, pretreatment with Cu-tryptophan (40 microM), a lipid-soluble scavenger of superoxide, provided no protective effect by itself, nor was there any potentiation of protection when combined with catalase. Further evidence implicating O2 metabolites in OA-induced edema was obtained by electron paramagnetic resonance (EPR) spectroscopy of perfusate samples to which the spin trap, sodium 3,5-dibromo-4-nitrosobenzenesulfonate (10 mM), was added. Analysis of these samples revealed the presence of free radicals after OA. Pretreatment with catalase (1,000 U/ml) and superoxide dismutase (250 U/ml) attenuated the EPR signal, indicating that proximal formation of O2 free radicals was in part responsible for the signal. These results suggest that reactive O2 metabolites are mediators of OA-induced pulmonary edema in the isolated perfused rabbit lung.

Animals↗
PubMed1989

Measurement of the unbound fraction of long chain nonesterified fatty acids (NEFA) in serum: methodological considerations.

Long-chain nonesterified fatty acids (NEFA) are extensively bound to albumin; knowledge of their unbound concentrations is important in evaluating the numerous biologic effects attributed to these compounds. We measured the unbound fraction of five long-chain NEFA in serum using the equilibrium partition of 14C-NEFA between heptane and aqueous phases. Commercial 14C-NEFA preparations gave non-linear estimates of unbound fraction with serum dilution, consistent with the presence of polar tracer impurities, but 14C-NEFA purified by alkaline ethanol extraction gave an approximately linear relationship between unbound fraction and serum dilution over a 4096-fold range of dilution, provided that pH of the aqueous phase remained stable. Mean unbound percentages were: myristic acid 0.0066, linolenic acid 0.0019, arachidonic acid 0.0017, oleic acid 0.00078 and palmitic acid 0.00061. These data suggest that some previous studies appear to have overestimated the free fraction of long-chain NEFA at physiological albumin concentrations by at least one order of magnitude.

Arachidonic Acids↗
PubMedDate not supplied

Fatty acid profile, tocopherol, squalene and phytosterol content of brazil, pecan, pine, pistachio and cashew nuts.

Nuts contain bioactive constituents that elicit cardio-protective effects including phytosterols, tocopherols and squalene. The objective of the present study was to determine the total oil content, peroxide value, fatty acid composition and levels of tocopherols, squalene and phytosterols in oil extracted from freshly ground brazil, pecan, pine, pistachio and cashew nuts. The total oil content of the nuts ranged from 40.4 to 60.8% (w/w) while the peroxide values ranged from 0.14 to 0.22 mEq O2/kg oil. The most abundant monounsaturated fatty acid was oleic acid (C18:1), while linoleic acid (C18:2) was the most prevalent polyunsaturated fatty acid. The levels of total tocopherols ranged from 60.8 to 291.0 mg/g. Squalene ranged from 39.5 mg/g oil in the pine nut to 1377.8 mg/g oil in the brazil nut. beta-Sitosterol was the most prevalent phytosterol, ranging in concentration from 1325.4 to 4685.9 mg/g oil. In conclusion, the present data indicate that nuts are a good dietary source of unsaturated fatty acids, tocopherols, squalene and phytosterols.

Anacardium↗
PubMed1992

Effect of mean airway pressure on bronchial mucosal blood flow in rabbits with oleic acid-induced injury.

The effects of mean airway pressure (MAP) on bronchial mucosal blood flow at the carina in nine anesthetized adult rabbits undergoing high frequency ventilation were studied. The animals were given oleic acid to diminish lung compliance and to exclude the influences of increasing MAP on systemic venous return. Mucosal blood flow decreased significantly when MAP exceeded 14 cmH2O. Mucosal blood velocity tended to decrease as higher levels of MAP were applied. Mucosal blood volume decreased significantly when MAP exceeded 20 cmH2O. Hemodynamics, arterial blood gas values and pH were not changed significantly. Our data demonstrate that bronchial mucosal blood flow decreases at high levels of MAP even if cardiac output remains constant. Hence this decrease of bronchial mucosal blood flow may be due to the transmission of pressure to submucosal bronchial capillaries.

Animals↗
PubMed2006

A comparison of intestinal lymphatic transport and systemic bioavailability of saquinavir from three lipid-based formulations in the anaesthetised rat model.

Saquinavir is a lipophilic, poorly water-soluble HIV protease inhibitor that undergoes extensive first-pass metabolism and exhibits poor oral bioavailability. Redirection of the absorption pathway of anti-HIV compounds from the portal blood to the HIV-rich intestinal lymphatics may enhance therapeutic efficacy and reduce the extent of the first-pass effect. This study investigates the potential of targeted intestinal lymphatic transport of saquinavir via a lipid formulation approach. Three formulations containing oleic acid were examined: cremophor-oleic acid mixed micelles, D-alpha tocopheryl polyethylene glycol 1000 succinate (TPGS)-oleic acid mixed micelles and an oleic acid microemulsion. The mesenteric lymph duct cannulated anaesthetised rat model was employed. Plasma and lymph samples were analysed by HPLC. Lymph triglyceride was measured using an enzymatic colorimetric technique. The extent of lymphatic transport from the lipid vehicles was 0.025-0.05% of the dose administered. The microemulsion produced higher and more prolonged mesenteric lymph concentrations than the micellar formulations. A strong correlation existed between the concentration of saquinavir in intestinal lymph and lymph triglyceride levels. The systemic bioavailability was estimated to be 8.5% and 4.8% for the cremophor mixed micelle and the microemulsion, respectively. The cremophor mixed micelles produced higher bioavailability than TPGS mixed micelles, implying that the nature of the surfactant can influence the distribution of drug between lymph and plasma.

Anesthesia↗
PubMed1997

Metallothionein-IIA promoter induction alters rat intestinal fatty acid binding protein expression, fatty acid uptake, and lipid metabolism in transfected L-cells.

Mouse L-cell fibroblasts, transfected with the cDNA encoding for rat intestinal fatty acid-binding protein (I-FABP) under the control of the human metallothionein-IIA promoter, were tested for their protein inducibility by the heavy metals cadmium (Cd2+) and zinc (Zn2+). I-FABP levels were quantitated by Western immunoblotting. Expression of I-FABP in all transfected cell lines tested was induced several-fold by optimized levels of Cd2+ and Zn2+. Induction conditions had no effect on cell growth rates or cell densities for any of the cell lines. Induction of high I-FABP-expressing cells (H141) decreased the initial rate and extent of uptake of cis-parinaric acid, a nonmetabolizable fatty acid, and of [3H]oleic acid, an esterifiable fatty acid. These effects of induction were specific for I-FABP-expressing cells since they were not observed in control cells or cells expressing a high level of liver (L-) FABP. Induction of H141 cells also significantly altered the esterification and distribution of exogenous [3H]oleic acid, especially among triglycerides and phosphatidylcholine, but less so among other glycero-phospholipids, cholesteryl esters, and phosphatidylethanolamine. Induction of H141 cells normalized [3H]oleic acid esterification into cholesteryl esters, phosphatidylcholine, total neutral lipids, and total phospholipids such that they no longer differed from control levels. In contrast, induction did not normalize [3H]oleic acid esterification into triacylglycerols and phosphatidylethanolamine to control levels in H141 cells; both remained significantly increased over control cells. Therefore, promoter induction levels of Cd2+ and Zn2+ enhanced I-FABP expression in H141 cells, thereby modulating both fatty acid uptake and intracellular esterification into neutral and phospholipids.

Animals↗
PubMed1992

Intestinal microcirculatory changes during fat absorption and the effect of cholecystokinin inhibitor.

The major objective of this study was to estimate how microvascular changes occur in the intestinal segment in relation to fat absorption and also to assess the role played by cholecystokinin (CCK) in fat-induced intestinal hyperemia. A 12-cm loop of rat middle small intestine was exposed to a 120-min infusion of oleic acid micelle solution containing [14C]oleic acid. Time-course changes of vascular diameter and red blood cell (RBC) velocity of submucosal arterioles, venules, and periglandular and muscular capillaries were determined simultaneously in their different order of branching by using intravital microscopy equipped with a high-speed video camera system. Lymphatic transport of oleic acid was also monitored by collecting lymph from intestinal lymphatics. The instillation of micelle produced significant dilatation of submucosal arterioles and venules and significant increase in RBC velocity in submucosal microvessels and periglandular capillaries at 15 to 30 min after the fat instillation. This corresponds well to the appearance of [14C]oleic acid in intestinal lymph. This microvascular dilatation and RBC velocity increase continued throughout the exposure to fat and started to attenuate 30 min after restoration to saline infusion. There was also heterogeneity in microvascular responses among different orders of branches to fat administration, and RBC velocity increase was not observed in muscular capillaries. Local intra-arterial infusion of CCK inhibitor, loxiglumide (CR 1505, 10 mg.kg-1.h-1), significantly attenuated both fat-induced microvascular dilatation and RBC velocity increase but not the fat absorptive function. Our results indicate that CCK plays a significant role in intestinal hyperemia induced by fat absorption. However, CCK-mediated intestinal microvascular change was not a prerequisite for fat absorption.

Animals↗
PubMed2001

Allosteric modulation of the human 5-HT(7A) receptor by lipidic amphipathic compounds.

Human 5-HT7A receptors positively modulated adenylyl cyclases via Gs subtypes of G proteins in human embryonic kidney 293 cells, and bound 5-hydroxytryptamine (HT) with high and low affinity (K(I) values of 1.5 +/- 0.3 and 93 +/- 4 nM). More than 60% of 5-HT7A receptors, however, displayed the high-affinity 5-HT binding with no sensitivity to 5'-guanylylimidodiphosphate. In this study, we found that select amphipathic agents affected the high-affinity 5-HT binding to 5-HT7A. Oleic acid at low concentrations (<15 microM), but not palmitic, stearic, and arachidonic acids, increased maximal [3H]5-HT binding without affecting its K(D) value and [3H]mesulergine (antagonist) binding. Fatty acid-free bovine serum albumin (FF-BSA), a scavenger of fatty acids and lipid metabolites, substantially reduced maximal [3H]5-HT binding (no change in K(D) value and antagonist binding) but lost its action upon treatment with inactive stearic acid. FF-BSA and oleic acid produced no appreciable effects on [3H]5-HT binding to analogous 5-HT receptors 5-HT1D and 5-HT2C. Among various lysophospholipids, lysophosphatidyl choline (50 microM) decreased maximal [3H]5-HT binding, and a similar zwitterion, 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate (CHAPS; 0.1%), increased it (no change in K(D)). Functionally, 5-HT-induced guanosine-5'-O-(3-[35S]thio)triphosphate (GTPgamma35S) binding was enhanced by oleic acid and CHAPS, but reduced by FF-BSA and lysophosphatidyl choline; the amphipathic agents and FF-BSA did not affect dopamine-induced GTPgamma35S binding at D1, a prototypic Gs-coupled receptor. At 5-HT7A, oleic acid, FF-BSA, CHAPS, and lysophosphatidyl choline also brought about corresponding changes in the half-maximal 5-HT concentration for cAMP production, without affecting the maximal and basal levels. We propose that endogenous, amphipathic lipid metabolites may modulate 5-HT7A receptors allosterically to promote high-affinity 5-HT binding and to enable receptors to couple more efficiently to Gs subtypes of G proteins.

Allosteric Regulation↗
PubMed1991

Glucose-responsive and oleic acid-responsive elements in the gene encoding the peroxisomal trifunctional enzyme of Candida tropicalis.

We have investigated the regulation of expression of the gene (HDE), encoding the peroxisomal trifunctional enzyme hydratase-dehydrogenase-epimerase (HDE), of the diploid yeast Candida tropicalis. Heterologous expression in Saccharomyces cerevisiae of constructs containing deletions in the upstream region of the HDE gene has allowed for determination of regions responsible for the control of expression of the HDE gene. Expression was monitored by immunoblot analysis of yeast lysates with anti-HDE serum. Regions have been identified that are responsible for both repression by glucose and induction by oleic acid. A glucose-responsive region lies between nucleotides (nt) -526 and -393. An oleic acid-responsive region lies between nt -393 and -341. An additional region controlling derepression by nonfermentable carbon sources is located downstream from nt -341. Comparison of the nt sequences of these regions to upstream regions of other oleic acid-responsive genes of C. tropicalis has identified possible consensus nt sequences for glucose- and oleic acid-responsive upstream elements in these genes. The regulation of the HDE gene in S. cerevisiae closely resembles that found in C. tropicalis, suggesting that similar mechanisms of transcriptional control operate in both yeasts.

3-Hydroxyacyl CoA Dehydrogenases↗
PubMed1992

[Antimutagenic substances in the Armeniacae semen and Persicae semen].

Using the Ames/Salmonella/microsome assay, we examined the antimutagenic effect of the hexane extract of Armeniacae semen (apricot (Prunus armeniaca L.) seed), Persicae semen (peach (P. persica Bat.) seed), and seeds of cherry (P. avium L.), plum (P. salicina Lindle) and almond (P. dulcis Mill). Hexane extracts of Armeniacae semen and Persicae semen inhibited the mutagenicity of benzo[a]pyrene (B[a]P), but those of seeds of cherry, plum and almond did not. The mutagenicities of 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) and 2-(2-furyl)-3-(5-nitro-2-furyl)acrylamide (AF-2) were also inhibited by the extracts of Armeniacae semen and Persicae semen. Inhibitory substances in Persicae semen were fractionated by silica gel column chromatography and high performance liquid chromatography, and were identified as oleic acid and linoleic acid. The contents of oleic acid and linoleic acid were 0.7 and 0.4% in the hexane extract of Armeniacae semen, and 1.5 and 0.5% in that of Persicae semen, respectively.

Antimutagenic Agents↗
PubMed1994

A functional and morphologic analysis of pressure-controlled inverse ratio ventilation in oleic acid-induced lung injury.

STUDY OBJECTIVE: To compare volume-controlled ventilation (VCV PEEP) with pressure-controlled inverse ratio ventilation (PCIRV) at equal levels of end-expiratory pressure. DESIGN: Animal study using an oleic acid lung injury model with random application of VCV PEEP and PCIRV. SETTING: Experimental laboratory investigation at the Department of Clinical Physiology at Uppsala University. ANIMALS: Twelve pigs. INTERVENTIONS: VCV PEEP and PCIRV at an end-expiratory pressure level of 10 cm H2O. MEASUREMENTS AND RESULTS: Lung mechanics, hemodynamics, and gas exchange. Recruitment of lung tissue, regional lung density, and distribution of inspired gas by computed tomography. Mean and peak airway pressures were 29 and 35 cm H2O with PCIRV and 17 and 45 cm H2O with VCV PEEP. Cardiac output and mean systemic blood pressure were lower with PCIRV (2.5 L/min and 82 mm Hg) than with VCV PEEP (3.1 L/min and 97 mm Hg). Physiologic dead space was 24 percent with VCV PEEP and 20 percent with PCIRV. Static compliance, arterial oxygen tension, and functional residual capacity were equal between the two ventilatory modes. End-expiratory, end-inspiratory, and dynamic computed tomographic densities were equal between VCV PEEP and PCIRV. Nonaerated and poorly aerated lung areas were of equal size with VCV PEEP and PCIRV. CONCLUSIONS: PCIRV was no better than VCV with similar PEEP levels in alveolar recruitment and aeration of the lung tissues or in oxygenating the blood. Cardiac output was lower with PCIRV than with VCV, causing lower oxygen delivery to peripheral tissues. PCIRV does allow for a reduction in minute ventilation and for lowering peak airway pressure.

Analysis of Variance↗
PubMed2002

Long-term overexpression of membrane type-1 matrix metalloproteinase and matrix metalloproteinase-2 in oleic acid-induced pancreatitis in rats.

INTRODUCTION: The matrix metalloproteinase (MMP) plays important roles in extracellular matrix turnover. However, little is known about the roles of MMP-2 and type IV collagen, and the relationship between MMP-2 and membrane type-1 matrix metalloproteinase (MT1-MMP) during progressive destruction of acinar cells in pancreatitis. AIMS AND METHODOLOGY: To examine the serial changes in the expression and activity of MMP-2 and expression of MT1-MMP and tissue inhibitor of matrix metalloproteinase-2 (TIMP-2) in rats after induction of pancreatitis by intraductal infusion of oleic acid, and to determine protein concentrations by Western blot analysis and localization of type IV collagen by immunostaining. RESULTS: Gelatinolytic activity of pro-and active MMP-2 and concentrations of MT1-MMP protein, as determined by zymography and Western blot analysis, respectively, increased significantly from 6 hours to day 42 after intraductal infusion of oleic acid. TIMP-2 mRNA expression was significantly higher than that at time 0 throughout the study period, and gelatinolytic activity of active MMP-2 increased from day 3 to day 42. In addition, immunoreactivity for type IV collagen was detected as a discontinuous line along the basement membranes of ducts, vessels, tubular complexes, and acinar cells. CONCLUSION: Our findings indicate that long-term increases of gelatinolytic activity of active MMP-2 cause continuous disorganization of type IV collagen in basement membranes during progressive atrophy of pancreatic gland in oleic acid-induced pancreatitis, and that MT1-MMP and TIMP-2 work as activating factors during proMMP-2 activation. Moreover, basement membranes disorganization in the sustentacula of acinar cells and duct epithelia seems to participate in continuous derangement of acinar cells and duct epithelium.

Animals↗
PubMed2001

Expression of fungal desaturase genes in cultured mammalian cells.

Long-chain polyunsaturated fatty acids (LC-PUFA) are important components of cellular structure and function. Most of LC-PUFA are derived from linoleic acid and alpha-linolenic acid. In plants and fungi, these two acids can be synthesized from oleic acid via the action of two enzymes, delta12 and delta15-desaturases. Due to lack of these enzymatic activities and the ability to synthesize these two essential fatty acids, animals must obtain them from the diet. In this report, we demonstrated the expression of a fungal delta12-desaturase gene in mouse L cells incubated in serum-free medium. The results showed a significant increase in the amount of linoleic acid with a concomitant decrease of oleic acid in cellular lipids. Most of the newly formed linoleic acid was incorporated into cellular phospholipids, particularly phosphatidylcholine. The increase of linoleic acid provided the substrate for the endogenous synthesis of (n-6) LC-PUFA, such as eicosadienoic acid (EDA), dihomo-gamma-linoleic acid (DGLA) and arachidonic acid (AA). Prolonged incubation further increased the levels of linoleic acid derived from oleic acid by the action of delta12-desaturase, and the levels of 20:2n-6 produced from linoleic acid by the action of the endogenous elongase. However, prolonged incubation suppressed significantly the formation of DGLA and AA. In a separate study, a fungal delta6-desaturase gene has also been expressed in the mouse L cells incubated in serum-containing medium. The result shows a significant increase in levels of 20:3n-6 and 20:4n-6. These findings demonstrate that through genetic modification, it is possible to (1) generate cell lines which no longer require dietary 'essential' fatty acids and (2) alter the endogenous fatty acid metabolism to enhance the production of LC-PUFA and their derivatives.

Animals↗