Papers by Cecil Pace-asciak
A low a-linolenic intake during early life increases adiposity in the adult guinea pig
Frontiers in Pharmacology
The edible catfish Arius bilineatus, (Valenciennes) elaborates a proteinaceous gel-like material ... more The edible catfish Arius bilineatus, (Valenciennes) elaborates a proteinaceous gel-like material through its epidermis when threatened or injured. Our on-going studies on this gel have shown it to be a complex mixture of several biologically active molecules. Anti-cancer studies on lipid fractions isolated from the gel-like materials showed them to be active against several cancer cell lines. This prompted us to investigate further the lipid composition of the catfish epidermal gel secretions (EGS). Analysis of the lipid fraction of EGS resulted in identification of 12 oxysterols including cholesterol and 2 deoxygenated steroids i.e., 7α-hydroxy cholesterol, 7β-hydroxycholesterol, 5,6 epoxycholesterol, 3β-hydroxycholest-5-ene-7-one and cholesta-3,5-dien-7-one. Progesterone, cholest-3,5-diene, cholesta-2,4-diene, cholest-3,5,6-triol and 4-cholesten-3-one were found as minor components, and were identified through their MS, 1HNMR and FTIR spectral data and were compared with those of ...
Copyright © 2015 David N. Douda et al.This is an open access article distributed under theCreativ... more Copyright © 2015 David N. Douda et al.This is an open access article distributed under theCreativeCommonsAttribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Pulmonary exacerbations in cystic fibrosis airways are accompanied by inflammation, neutrophilia, andmucous thickening. Cystic fibrosis sputum contains a large amount of uncleared DNA contributed by neutrophil extracellular trap (NET) formation from neutrophils. The exact mechanisms of the induction of NETosis in cystic fibrosis airways remain unclear, especially in uninfected lungs of patients with early cystic fibrosis lung disease. Here we show that Hepoxilin A3, a proinflammatory eicosanoid, and the synthetic analog of Hepoxilin B3, PBT-3, directly induce NETosis in human neutrophils. Furthermore, we show that Hepoxilin A3-mediated NETosis is NADPH-oxidase-dependent at lower doses of Hepoxilin A3, while it is NADPH-oxidase-independen...
Nutrition & Metabolism, 2010
Background: The composition of dietary fatty acids (FA) during early life may impact adult adipos... more Background: The composition of dietary fatty acids (FA) during early life may impact adult adipose tissue (AT) development. We investigated the effects of α-linolenic acid (ALA) intake during the suckling/weaning period on AT development and metabolic markers in the guinea pig (GP). Methods: Newborn GP were fed a 27%-fat diet (w/w %) with high (10%-ALA group), moderate (2.4%-ALA group) or low (0.8%-ALA group) ALA content (w/w % as total FA) until they were 21 days old (d21). Then all animals were switched to a 15%-fat diet containing 2% ALA (as total FA) until 136 days of age (d136). Results: ALA and docosapentaenoic acid measured in plasma triglycerides (TG) at d21 decreased with decreasing ALA intake. Total body fat mass was not different between groups at d21. Adipose tissue TG synthesis rates and proliferation rate of total adipose cells, as assessed by 2 H 2 O labelling, were unchanged between groups at d21, while hepatic de novo lipogenesis was significantly 2-fold increased in the 0.8%-ALA group. In older GP, the 0.8%-ALA group showed a significant 15-%-increased total fat mass (d79 and d107, p < 0.01) and epididymal AT weight (d136) and tended to show higher insulinemia compared to the 10%-ALA group. In addition, proliferation rate of cells in the subcutaneous AT was higher in the 0.8%-ALA (15.2 ± 1.3% new cells/5d) than in the 10%-ALA group (8.6 ± 1.7% new cells/5d, p = 0.021) at d136. AT eicosanoid profiles were not associated with the increase of AT cell proliferation. Conclusion: A low ALA intake during early postnatal life promotes an increased adiposity in the adult GP.
AJP: Lung Cellular and Molecular Physiology, 2006
Mechanical ventilation is the primary supportive treatment for infants and adults suffering from ... more Mechanical ventilation is the primary supportive treatment for infants and adults suffering from severe respiratory failure. Adverse mechanical ventilation (overdistension of the lung) triggers a proinflammatory response. Along with cytokines, inflammatory mediators such as bioactive lipids are involved in the regulation of the inflammatory response. The arachidonic acid pathway is a key source of bioactive lipid mediators, including prostanoids. Although ventilation has been shown to influence the production of prostanoids in the lung, the mechanotransduction pathways are unknown. Herein, we established that cyclic stretch of fetal lung epithelial cells, but not fibroblasts, can evoke an extremely sensitive, rapid alteration in eicosanoid metabolism through a cyclooxygenase (COX)-2 dependent mechanism. Cyclic stretch significantly increased PGI2, PGF2α, PGD2, PGE2, and thromboxane B2 levels in the media of epithelial cells, but did not alter leukotriene B4 or 12-hydroxyeicosatetrae...
Cancers
Identifying novel anti-cancer drugs is important for devising better cancer treatment options. In... more Identifying novel anti-cancer drugs is important for devising better cancer treatment options. In a series of studies designed to identify novel therapeutic compounds, we recently showed that a C-20 fatty acid (12,15-epoxy-13,14-dimethyleicosa-12,14-dienoic acid, a furanoic acid or F-6) present in the lipid fraction of the secretions of the Arabian Gulf catfish skin (Arius bilineatus Val.; AGCS) robustly induces neutrophil extracellular trap formation. Here, we demonstrate that a lipid mix (Ft-3) extracted from AGCS and F-6, a component of Ft-3, dose dependently kill two cancer cell lines (leukemic K-562 and breast MDA MB-231). Pure F-6 is approximately 3.5 to 16 times more effective than Ft-3 in killing these cancer cells, respectively. Multiplex assays and network analyses show that F-6 promotes the activation of MAPKs such as Erk, JNK, and p38, and specifically suppresses JNK-mediated c-Jun activation necessary for AP-1-mediated cell survival pathways. In both cell lines, F-6 sup...
Lipids in Health and Disease, 2013
Background: Inflammatory bowel diseases (IBD) are chronic intestinal inflammatory diseases affect... more Background: Inflammatory bowel diseases (IBD) are chronic intestinal inflammatory diseases affecting about 1% of western populations. New eating behaviors might contribute to the global emergence of IBD. Although the immunoregulatory effects of omega-3 fatty acids have been well characterized in vitro, their role in IBD is controversial. Methods: The aim of this study was to assess the impact of increased fish oil intake on colonic gene expression, eicosanoid metabolism and development of colitis in a mouse model of IBD. Rag-2 deficient mice were fed fish oil (FO) enriched in omega-3 fatty acids i.e. EPA and DHA or control diet for 4 weeks before colitis induction by adoptive transfer of naïve T cells and maintained in the same diet for 4 additional weeks. Onset of colitis was monitored by colonoscopy and further confirmed by immunological examinations. Whole genome expression profiling was made and eicosanoids were measured by HPLC-MS/MS in colonic samples. Results: A significant reduction of colonic proinflammatory eicosanoids in FO fed mice compared to control was observed. However, neither alteration of colonic gene expression signature nor reduction in IBD scores was observed under FO diet. Conclusion: Thus, increased intake of dietary FO did not prevent experimental colitis.
Frontiers in Pharmacology
The authors studied the production of radioimmunoassayable (i-) 6-K-PGEâ - a potent renin secret... more The authors studied the production of radioimmunoassayable (i-) 6-K-PGEâ - a potent renin secretagogue, vasodilator and platelet anti-aggregatory agent - in the rabbit isolated kidney perfused at 2 ml/g/min with a modified Krebs'-Henseleit solution (37°C). The ureter was cannulated, enabling separate collections or urinary and venous effluents. 6-K-PGEâ levels were determined by RIA after acidic lipid extraction and high performance
Journal of chromatography. B, Biomedical sciences and applications
Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism, 1977
Homogenates of the lamb ductus arteriosus at term have the capacity to convert exogenous arachido... more Homogenates of the lamb ductus arteriosus at term have the capacity to convert exogenous arachidonic acid into prostaglandins Ez, Fza and 6-ketoprostaglandin F ,ol. No evidence was obtained for the formation of prostaglandin Dz and thromboxane Bz. All products were quantitated by mass spectrometry. 6-Ketoprostaglandin F ia was the major compound, formed in amounts in excess of 10 fold over prostaglandins Ez and F,, .
Journal of Chromatography B: Biomedical Sciences and Applications, 2001
We report herein an improved method for the high-performance liquid chromatographic separation an... more We report herein an improved method for the high-performance liquid chromatographic separation and analysis of eicosanoids formed during the stimulation of human platelets in vitro with collagen. Since the products of interest, excepting arachidonic acid, contain hydroxyl groups (one to several), our method involves the conversion of the hydroxyl groups into acetates (pyridine/acetic anhydride) after derivatization with anthryl diazomethane (ADAM)
Journal of Chromatography B: Biomedical Sciences and Applications, 2001
Biochimica et biophysica acta, Jan 30, 1978
Five prostaglandins, i.e. prostaglandins E2, F2alpha and D2, 6-keto-prostaglandin F1alpha and thr... more Five prostaglandins, i.e. prostaglandins E2, F2alpha and D2, 6-keto-prostaglandin F1alpha and thromboxane B2, were measured by mass spectrometry. Homogenates of fetal lamb brain, lung, liver, spleen and kidney and the ductus arteriosus, aorta and pulmonary artery formed different amounts of each product. Although the main prostaglandin in the fetal organs was prostaglandin E2, arterial tissue formed mostly 6-keto-prostaglandin F1alpha. These results demonstrate significant differences between organs and tissues in the relative direction of the 'prostaglandin synthetase' enzyme complex.
Biochimica et biophysica acta, Jan 28, 1978
Homogenates of tissues from fetal and neonatal lamb ductus arteriosus, aorta and pulmonary artery... more Homogenates of tissues from fetal and neonatal lamb ductus arteriosus, aorta and pulmonary artery have the capacity to convert arachidonic acid as well as the intermediate prostaglandin endoperoxide, prostaglandin H2, into three products: prostaglandins E2, F2alpha and a major product 6-ketoprostaglandin F1alpha. The three tissues also displayed prostaglandin 15-hydroxydehydrogenase and 13-reductase catabolic activities. The catabolishing system showed considerable substrate specificity: prostaglandin E1 was a good substrate whereas prostaglandins F1alpha and F2alpha were completely devoid of catabolism. The complete system was observed in immature as well as mature arterial vessels, in the fetus as well as the neonate (up to 7 days old). These experiments demonstrate the presence of several components of the prostaglandin system in these tissues and offer biochemical evidence for the implication of prostaglandins E2 and I2 in the maintenance of the ductus and neighboring vessels in...
FEBS Letters, 2002
We have previously shown that PBT-3, a stable synthetic analog of hepoxilins, inhibits the aggreg... more We have previously shown that PBT-3, a stable synthetic analog of hepoxilins, inhibits the aggregation of human platelets in vitro evoked by collagen through inhibition of thromboxane A(2) formation and action on the TP receptor. We now show that PBT-3 is capable of potently inhibiting the second phase of aggregation evoked by ADP in both washed human platelets and platelet-rich plasma (PRP), a phase associated with thromboxane formation. Aspirin blocks this second phase as well; so does the thromboxane receptor antagonist SQ 29,548. When ADP-evoked aggregation in PRP is activated by heparin through an enhancement of thromboxane formation, PBT-3, aspirin as well as SQ 29,548 block this activation through different mechanisms. These data confirm the inhibitory action of PBT-3 on aggregation of human platelets through inhibition of both thromboxane formation and blockade of thromboxane receptor action and suggest that this family of compounds may be useful in the treatment of thrombotic disorders in combination with heparin.
Biochemistry and Cell Biology, 1983
Intact rings and slices of ductus arteriosus from fetal lambs near term (130–143 days gestation) ... more Intact rings and slices of ductus arteriosus from fetal lambs near term (130–143 days gestation) were incubated with [14C]arachidonic acid and the fate of the label in the incubation fluid and tissue was followed by thin-layer radiochromatography (TLC). Prostaglandins formed from endogenous stores of arachidonic acid were assayed by capillary gas chromatography with electron-capture detection. In additional experiments, the prelabelled tissue was incubated with various drugs (e.g., angiotensin II, bradykinin, and calcium ionophore) to determine their effects on the release of 14C-labelled prostaglandins. Results indicate that the ductus arteriosus is oriented towards forming prostaglandin (PG) I2, with PGE2 being formed to a minor extent in all studies. While radiochromatographic studies (TLC) suggested a considerable complexity mostly because of overlapping products (PGs and metabolites), this was resolved using gas chromatography where a complete resolution of PGs from these metab...
Anesthesiology, 2005
Background Atelectasis results in impaired compliance and gas exchange and, in extreme cases, inc... more Background Atelectasis results in impaired compliance and gas exchange and, in extreme cases, increased microvascular permeability, pulmonary hypertension, and right ventricular dysfunction. It is not known whether such atelectasis-induced lung injury is due to the direct mechanical effects of lung volume reduction and alveolar collapse or due to the associated regional lung hypoxia. The authors hypothesized that addition of supplemental oxygen to an atelectasis-prone ventilation strategy would attenuate the pulmonary vascular effects and reduce the local levels of vasoconstrictor eicosanoids. Methods In series 1, anesthetized, atelectasis-prone mechanically ventilated rats were randomly assigned to one of six groups based on the inspired oxygen concentration and ventilated without recruitment. Series 2 was performed to determine the cardiac and pulmonary vascular effects of 21% versus 100% inspired oxygen. In series 3, computed tomography scans were performed after ventilation with...
Biomolecules
Various biomolecules induce neutrophil extracellular trap (NET) formation or NETosis. However, th... more Various biomolecules induce neutrophil extracellular trap (NET) formation or NETosis. However, the effect of fatty acids on NETosis has not been clearly established. In this study, we focused on the NETosis-inducing ability of several lipid molecules. We extracted the lipid molecules present in Arabian Gulf catfish (Arius bilineatus, Val) skin gel, which has multiple therapeutic activities. Gas chromatography–mass spectrometry (GC-MS) analysis of the lipid fraction-3 from the gel with NETosis-inducing activity contained fatty acids including a furanoid F-acid (F6; 12,15-epoxy-13,14-dimethyleicosa-12,14-dienoic acid) and common long-chain fatty acids such as palmitic acid (PA; C16:0), palmitoleic acid (PO; C16:1), stearic acid (SA; C18:0), and oleic acid (OA; C18:1). Using pure molecules, we show that all of these fatty acids induce NETosis to different degrees in a dose-dependent fashion. Notably, F6 induces a unique form of NETosis that is rapid and induces reactive oxygen species ...
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Papers by Cecil Pace-asciak