Journal of lipid mediators and cell signalling最新文献

{"title":"Effects of ω3 fatty acids on receptor tyrosine kinase and PLC activities in EMT6 cells","authors":"Karen C Estes,&nbsp;Brian T Rose,&nbsp;Jamie J Speck,&nbsp;Melvin L Nutter,&nbsp;Ronald C Reitz","doi":"10.1016/S0929-7855(97)00022-9","DOIUrl":"10.1016/S0929-7855(97)00022-9","url":null,"abstract":"<div><p>The effects of <em>ω</em><span>3 fatty acids and epidermal growth factor<span> (EGF) on the activity of receptor tyrosine kinase (RTK) and phospholipase C (phosphatidylinositol (PI)-specific PLC) were examined in EMT6 cells. The non-</span></span><em>ω</em>3 treated, non-EGF stimulated cells served as controls. Treatment of the EMT6 cells with <em>ω</em>3 fatty acids resulted in a 62% increase in RTK activity and a 67% increase in PI-specific PLC activity. When EGF was added to incubations for RTK activity, it stimulated the RTK activity 40% in the control cells and 130% in the <em>ω</em>3-treated cells. When EGF was added to incubations for PI-specific PLC activity, a 54% increase in PI-specific PLC activity was observed in control cells and a 94% increase in the <em>ω</em>3-treated cells. Thus, treating EMT6 cells with <em>ω</em><span>3 fatty acids seems to increase RTK activity and PI-specific PLC activity to a similar extent, but has differential effects on the ability of these enzyme activities to be stimulated by EGF.</span></p></div>","PeriodicalId":79347,"journal":{"name":"Journal of lipid mediators and cell signalling","volume":"17 2","pages":"Pages 81-96"},"PeriodicalIF":0.0,"publicationDate":"1997-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0929-7855(97)00022-9","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20385394","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhanced hepatic fatty acid oxidation and upregulated carnitine palmitoyltransferase II gene expression by methyl 3-thiaoctadeca-6,9,12,15-tetraenoate in rats","authors":"Nina Willumsen ,&nbsp;Hege Vaagenes ,&nbsp;Arild C Rustan ,&nbsp;Hans Grav ,&nbsp;Morten Lundquist ,&nbsp;Lars Skattebøl ,&nbsp;Jon Songstad ,&nbsp;Rolf K Berge","doi":"10.1016/S0929-7855(97)00024-2","DOIUrl":"10.1016/S0929-7855(97)00024-2","url":null,"abstract":"&lt;div&gt;&lt;p&gt;This study reports the effects of a novel polyunsaturated 3-thia fatty acid, methyl 3-thiaoctadeca-6,9,12,15-tetraenoate on serum lipids&lt;span&gt; and key enzymes in hepatic fatty acid metabolism compared to a saturated 3-thia fatty acid, tetradecylthioacetic acid. Palmitic acid treated rats served as controls. Fatty acids were administered by gavage in daily doses of 150 mg/kg body weight for 10 days.&lt;/span&gt;&lt;/p&gt;&lt;p&gt;&lt;span&gt;The aim of the present study was: (a) To investigate the effect of a polyunsaturated 3-thia fatty acid ester&lt;span&gt;&lt;span&gt;&lt;span&gt;, methyl 3-thiaoctadeca-6,9,12,15-tetraenoate on plasma lipids in normolipidemic rats; (b) to verify whether the lipid-lowering effect could be consistent with enhanced fatty acid oxidation; and (c) to study whether decreased activity of esterifying enzymes and diversion to &lt;/span&gt;phospholipid synthesis is a concerted mechanism in limiting the availability of &lt;/span&gt;free fatty acid as a substrate for hepatic &lt;/span&gt;&lt;/span&gt;triglyceride&lt;span&gt;&lt;span&gt; formation. Repeated administration&lt;span&gt; of the polyunsaturated 3-thia fatty acid ester for 10 days resulted in a reduction of plasma triglycerides (40%), cholesterol (33%) and phospholipids (20%) compared to controls. Administration of polyunsaturated and saturated 3-thia fatty acids (daily doses of 150 mg/kg body weight) reduced levels of lipids to a similar extent and followed about the same time-course. Both mitochondrial and peroxisomal fatty acid oxidation increased (1.4-fold- and 4.2-fold, respectively) and significantly increased activities of carnitine palmitoyltransferase (CPT) (1.6-fold), 2,4-dienoyl-CoA reductase (1.2-fold) and fatty acyl-CoA oxidase (3.0-fold) were observed in polyunsaturated 3-thia fatty acid treated animals. This was accompanied by increased CPT-II mRNA (1.7-fold), 2,4-dienoyl-CoA reductase mRNA (2.9-fold) and fatty acyl-CoA oxidase mRNA (1.7-fold). Compared to controls, the hepatic triglyceride &lt;/span&gt;&lt;/span&gt;biosynthesis&lt;span&gt;&lt;span&gt; was retarded as indicated by a decrease in liver triglyceride content (40%). The activities of glycerophosphate acyltransferase, acyl-CoA: 1,2-diacylglycerol acyltransferase and CTP:phosphocholine cytidylyltransferase were increased. The cholesterol lowering effect was accompanied by a reduction in HMG-CoA reductase activity (80%) and acyl-CoA:cholesterol acyltransferase activity (33%). In hepatocytes treated with methyl 3-thiaoctadeca-6,9,12,15-tetraenoate, fatty acid oxidation was increased 1.8-fold compared to controls. The results suggest that treatment with methyl 3-thiaoctadeca-6,9,12,15-tetraenoate reduces plasma triglycerides by a decrease in the availability of fatty acid substrate for triglyceride biosynthesis via enhanced fatty acid oxidation, most likely attributed to the mitochondrial fatty acid oxidation. It is hypothesized that decreased phosphatidate phosphohydrolase activity may be an additive mechanism which contribute whereby 3-thia fatty acids reduce triglyceride formation in the","PeriodicalId":79347,"journal":{"name":"Journal of lipid mediators and cell signalling","volume":"17 2","pages":"Pages 115-134"},"PeriodicalIF":0.0,"publicationDate":"1997-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0929-7855(97)00024-2","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20385863","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Altered intracellular calcium signalling after PAF stimulations in polymorphonuclear leukocytes from asthmatic patients","authors":"P. Bialasiewicz,&nbsp;D. Nowak,&nbsp;M. Krol,&nbsp;A. Antczak","doi":"10.1016/S0929-7855(97)00018-7","DOIUrl":"10.1016/S0929-7855(97)00018-7","url":null,"abstract":"<div><p>Platelet activating factor (PAF), a potent lipid mediator, has been implicated in the pathogenesis of airways inflammation in bronchial asthma. Binding of PAF to its receptor (Nakamura et al., 1991) leads to changes of intracellular Ca²⁺ concentration ([Ca²⁺]_<em>i</em>) that is crucial to cell activation. Therefore, the aim of our study was to investigate whether PMNL of asthmatic patients stimulated with PAF(10⁻⁷ M) differ in relation to changes of [Ca²⁺]_<em>i</em> from cells of healthy subjects. PMNL from asthmatic patients revealed attenuated first response to PAF stimulation—increase in [Ca²⁺]_<em>i</em> (A[Ca²⁺]_<em>i</em>) was 1.3-fold lower in cells of asthmatics (<em>P</em> &lt; 0.05) versus PMNL of healthy subjects. As determined in experiments with low extracellular calcium concentration, Ca²⁺ release from internal stores tended to be increased in asthmatics and hence the difference in total Ca²⁺ response was related to decrease in Ca²⁺ influx. Thus the contribution of Ca²⁺ from internal stores to the total first Ca²⁺ response upon PAF stimulation was two-fold higher (58 ± 18 vs. 29 ± 8%, <em>P</em> &lt; 0.001) in PMNL of asthmatics compared with healthy subjects. Two subsequent Ca²⁺ responses evoked by stimulations with the agonist in 1 mM Ca²⁺ buffer did not differ between study groups. In low Ca²⁺ buffer PMNL of 50% of asthmatics responded to the second stimulation while cells of healthy subjects remained unresponsive. The altered Ca²⁺ responses in PMNL of asthmatic subjects may reflect previous contact with mediator(s) that occur in vivo which may be at least partially explained by the phenomenon of down regulation reported for PAF receptor upon cell stimulation.</p></div>","PeriodicalId":79347,"journal":{"name":"Journal of lipid mediators and cell signalling","volume":"17 1","pages":"Pages 21-30"},"PeriodicalIF":0.0,"publicationDate":"1997-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0929-7855(97)00018-7","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20241808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of microsomal GST-II by Western blot and identification of a novel LTC4 isomer","authors":"Per-Johan Jakobsson ,&nbsp;Kylie A. Scoggan ,&nbsp;James Yergey ,&nbsp;Joseph A. Mancini ,&nbsp;Anthony W. Ford-Hutchinson","doi":"10.1016/S0929-7855(97)00013-8","DOIUrl":"10.1016/S0929-7855(97)00013-8","url":null,"abstract":"<div><p>Protein expression of microsomal GST-II and LTC₄ synthase was analyzed by Western blot. Correlation between a 17 kDa band and LTC₄ formation was observed for both enzymes. The expression of microsomal GST-II was several fold more efficient than the expression of LTC₄ synthase. In addition to catalyzing the biosynthesis of LTC₄, microsomal GST-II also produces another product, which has been subjected to mass spectrometric analysis. This analysis demonstrates that the novel product is an isomer of LTC₄.</p></div>","PeriodicalId":79347,"journal":{"name":"Journal of lipid mediators and cell signalling","volume":"17 1","pages":"Pages 15-19"},"PeriodicalIF":0.0,"publicationDate":"1997-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0929-7855(97)00013-8","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20241807","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of arachidonyltrifluoromethyl ketone on cytosolic [Ca2+] in HIT insulinoma cells","authors":"Douglas Stickle ,&nbsp;Sasanka Ramanadham ,&nbsp;John Turk","doi":"10.1016/S0929-7855(97)00012-6","DOIUrl":"10.1016/S0929-7855(97)00012-6","url":null,"abstract":"<div><p>Arachidonyltrifluoromethyl ketone (ATFMK), an analogue of arachidonic acid (AA), inhibits an 85 kDa cytosolic phospholipase A₂ enzyme. Exposure of HIT insulinoma cells to ATFMK induced a delayed, sustained, and irreversible increase in cytosolic [Ca²⁺] that required extracellular Ca²⁺ and a concentration-dependent inhibition of depolarization-induced increases in cytosolic [Ca²⁺] prior to onset of the delayed response to ATFMK. These results suggest a disruptive effect of ATFMK on calcium mobilization which may contribute to its effects on insulin secretion from β-cells.</p></div>","PeriodicalId":79347,"journal":{"name":"Journal of lipid mediators and cell signalling","volume":"17 1","pages":"Pages 65-70"},"PeriodicalIF":0.0,"publicationDate":"1997-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0929-7855(97)00012-6","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20242454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of endotoxin and platelet-activating factor on rat vascular permeability: role of vasoactive mediators","authors":"Dolors Balsa,&nbsp;Manuel Merlos,&nbsp;Marta Giral,&nbsp;Rosa Ferrando,&nbsp;Julian Garcia-Rafanell,&nbsp;Javier Forn","doi":"10.1016/S0929-7855(97)00019-9","DOIUrl":"10.1016/S0929-7855(97)00019-9","url":null,"abstract":"<div><p>The contribution of several vasoactive mediators such as histamine, serotonin, bradykinin, arachidonic acid metabolites and PAF to vascular permeability changes was determined in a rat model of acute endotoxemia. Lipopolysaccharide (10–40 mg/kg, i.v.) from <em>E. coli</em> 0127:138 (LPS) elicited an increase in Evans blue extravasation in trachea, thymus, seminal vesicle and stomach, whereas other organs remained unaffected. LPS (25 mg/kg)-induced extravasation was not inhibited by intravenous pretreatment with histamine (H₁) antagonist mepyramine (5 mg/kg) or bradykinin (B₂) antagonist HOE-140 (0.1 mg/kg), whereas other standard drugs selectively inhibited leakage in particular tissues, e.g. the cyclooxygenase inhibitor indomethacin (5 mg/kg) in trachea (78%) and seminal vesicle (64%), the serotonin and H₁ antagonist cyproheptadine (2 mg/kg) in trachea (88%) and stomach (56%) and the dual cyclooxygenase/lipoxygenase inhibitor phenidone (10 mg/kg) in seminal vesicle (87%). PAF antagonists lexipafant and UR-12460 (10 mg/kg), but not apafant, potently inhibited extravasation in trachea (59, 84%) and seminal vesicle (81, 78%) and in stomach only UR-12460 (52%), whereas all of them were ineffective in thymus. When extravasation was induced by PAF (4 μg/kg) a low dose (0.1 mg/kg) of the three PAF antagonists strongly reduced extravasation in thymus and seminal vesicle, whereas lexipafant and UR-12460 did so in trachea (82, 100%) and only lexipafant in stomach (100%). Mepyramine, cyproheptadine, HOE-140 and indomethacin did not inhibit the effect of PAF, whereas phenidone inhibited it by 58% in trachea. These results suggest that most of the LPS-induced increase in vascular permeability is mediated by secondary vasoactive mediators among which PAF plays a pivotal role, although their relative contribution may vary from tissue to tissue.</p></div>","PeriodicalId":79347,"journal":{"name":"Journal of lipid mediators and cell signalling","volume":"17 1","pages":"Pages 31-45"},"PeriodicalIF":0.0,"publicationDate":"1997-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0929-7855(97)00019-9","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20242452","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacological evidence for the putative existence of two different subtypes of PAF receptors on platelets and leukocytes; studies with yangambin","authors":"Jean-Marc Herbert ,&nbsp;Hugo C. Castro-Faria-Neto ,&nbsp;JoséM. Barbosa-Filho ,&nbsp;Renato S.B. Cordeiro ,&nbsp;Eduardo Tibiriça","doi":"10.1016/S0929-7855(97)00011-4","DOIUrl":"10.1016/S0929-7855(97)00011-4","url":null,"abstract":"<div><p>Yangambin, a new naturally-occuring platelet activating receptor (PAF) receptor antagonist competitively displaced [³H]-PAF from its high affinity binding sites on washed human platelets with a Ki value of 1.1 ± 0.3 μM (<em>n</em> = 3). Studies carried out in parallel demonstrated that SR 27417, a newly-developed PAF receptor antagonist also antagonized [³H]-PAF binding to these cells with a Ki value of 51 ± 2 pM. SR 27 417 (<em>N</em>-(2-dimethylamino ethyl)-<em>N</em>-(3-pyridinyl methyl) [4-(2,4,6-triisopropyl phenyl) thiazol-2-yl] amine) selectively and competitively inhibited the specific binding of [³H]-PAF on human polymorphonuclear leukocytes (Ki = 65 ± 5.2 pM) whereas high doses of yangambin remained ineffective. Yangambin inhibited PAF-induced aggregation of human platelets in vitro (IC₅₀ = 1.0 ± 0.2 μM) but had no effect PAF-induced oxidative burst in human polymorphonuclear leukocytes. In guinea pigs, yangambin inhibited PAF-induced thrombocytopenia but did not affect leukocytopenia whereas SR 27 417 afforded complete protection against both PAF-induced thrombocytopenia and leukocytopenia. In conclusion, yangambin discriminates between two different types of PAF receptors on platelets and polymorphonuclear leukocytes and can be considered as the first PAF receptor antagonist described to date exhibiting such an effect.</p></div>","PeriodicalId":79347,"journal":{"name":"Journal of lipid mediators and cell signalling","volume":"17 1","pages":"Pages 1-14"},"PeriodicalIF":0.0,"publicationDate":"1997-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0929-7855(97)00011-4","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20241806","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison of hexadecylphosphocholine with fish oil as an antitumor agent","authors":"Daniel T. Colombo,&nbsp;Lisa K. Tran,&nbsp;Jamie J. Speck,&nbsp;Ronald C. Reitz","doi":"10.1016/S0929-7855(97)00020-5","DOIUrl":"10.1016/S0929-7855(97)00020-5","url":null,"abstract":"<div><p>Hexadecylphosphocholine (HePC) reduced the growth of the human mammary tumor, MX-1, in the athymic nude mouse similar to the fish oil, MaxEPA. When used together, HePC and MaxEPA were additive towards reducing tumor growth. An unsaturated alkylphosphocholine mixture, ShisoPC, was not as effective as HePC in reducing tumor growth. MaxEPA reduced tumor PGE₂ levels greater than 90%, while HePC and the ShisoPC only reduced tumor PGE₂ 40–60% with HePC being slightly better than ShisoPC. MaxEPA markedly increased the cellular ω3 fatty acids and decreased 20:4ω6, the substrate for PGE₂. HePC did not alter the tumor fatty acid composition, but it significantly lowered the total fatty acid concentration of the tumor by about 47%. In addition, phosphatidylcholine and sphingomyelin decreased in tumors from animals treated with HePC, and alterations in other phospholipids also were noted. These data suggest that different mechanisms exist for HePC and fish oil in reducing tumor growth.</p></div>","PeriodicalId":79347,"journal":{"name":"Journal of lipid mediators and cell signalling","volume":"17 1","pages":"Pages 47-63"},"PeriodicalIF":0.0,"publicationDate":"1997-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0929-7855(97)00020-5","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20242453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Erratum to “Roles of phospholipases A2 in brain cell and tissue injury associated with ischemia and excitotoxicity” [J. Lip. Med. Cell Signal. 14 (1996) 15]","authors":"Joseph V Bonventre","doi":"10.1016/S0929-7855(97)00021-7","DOIUrl":"10.1016/S0929-7855(97)00021-7","url":null,"abstract":"<div><p>Phospholipase A₂ (PLA₂) activity is an important contributor to destructive cellular processes in the central nervous system. Two cytosolic forms of calcium dependent PLA₂ have been characterized in the gerbil brain and the neuronal cultures from rat brain. PLA₂ enzymatic activity in cell free extracts from cortical neuronal cultures is upregulated after cells are exposed to glutamate. Brief exposure to a calcium ionophore or phorbol 12-myristate 13-acetate (PMA) stably enhanced PLA₂ activity. Stable activation of the two cytosolic forms of PLA₂ occur prior to evidence of cell death and this activation is reversible. The larger molecular mass form was characterized as cPLA₂. The smaller form (∼ 14 kDa) was distinct from Group I and II PLA₂. Exposure to glutamate shifted the calcium activation curve of the smaller form to the left suggesting a novel mechanism of regulation of PLA₂. Glutamate-induced stable enhancement of PLA₂ activity, by processes involving calcium and protein kinase C activation, is a potential molecular switch likely mediating changes in synaptic function and contributing to excitotoxicity.</p></div>","PeriodicalId":79347,"journal":{"name":"Journal of lipid mediators and cell signalling","volume":"17 1","pages":"Pages 71-79"},"PeriodicalIF":0.0,"publicationDate":"1997-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0929-7855(97)00021-7","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20242455","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of a trans configuration for the apoptosis-inducing activity of ceramide","authors":"Etsu Kishida ,&nbsp;Megumi Kasahara ,&nbsp;Yumiko Takagi ,&nbsp;Masae Matsumura ,&nbsp;Takaomi Hayashi ,&nbsp;Shu Kobayashi ,&nbsp;Yasuo Masuzawa","doi":"10.1016/S0929-7855(97)00010-2","DOIUrl":"10.1016/S0929-7855(97)00010-2","url":null,"abstract":"<div><p>The requirement of a <em>trans</em><span> double bond for the biological action of ceramide was assessed by comparing the apoptosis-inducing activity of various ceramide analogs. The </span><em>cis</em><span><span> isomer and an acetylene type derivative of sphingosine were chemically synthesized, and the 2-amino moiety was acylated with </span>hexanoic acid. These cell-permeable ceramide derivatives were compared with </span><em>N</em>-hexanoyl sphingosine (C₆-Cer) or <em>N</em>-hexanoyl dihydrosphingosine (C₆-DH-Cer) in their activity to induce apoptosis of HL60. Either the <em>cis</em> isomer of C₆-Cer (C₆-<em>cis</em>-Cer) or a triple bond derivative (C₆<span>-TRP-Cer) induced apoptosis when assessed by fluorescence microscopy of the morphological changes and electrophoretic analysis of DNA C</span>₆<span>-TRP-Cer yielded the highest percentage of apoptotic cells corresponding to three times that was induced by C</span>₆-Cer. C₆-<em>cis</em>-Cer also showed stronger activity than C₆-Cer. The minimum amounts of C₆-TRP-Cer and C₆-<em>cis</em> derivative required to induce apoptosis were 0.1 and 0.5 <em>μ</em>M, respectively, while 1 <em>μ</em>M C₆-Cer was required to exhibit the activity. C₆-DH-Cer showed very low but significant activity above 10 <em>μ</em>M. <em>N</em>-acetyl-sphingosine (C₂-Cer) induced more apoptotic cells than C₆-Cer, and C₂-TRP-Cer was much more potent than C₂-Cer. These observations suggest that the <em>trans</em> configuration of ceramide is not necessarily essential for the activity to induce apoptosis. In addition, distinctive activity of C₆- or C₂-TRP-Cer suggests that this ceramide analog might be useful for developing a new type of antitumor drug.</p></div>","PeriodicalId":79347,"journal":{"name":"Journal of lipid mediators and cell signalling","volume":"16 3","pages":"Pages 127-137"},"PeriodicalIF":0.0,"publicationDate":"1997-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0929-7855(97)00010-2","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20188896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}