Journal of lipid mediators最新文献_第9页

Ca(2+)-sensitive cytosolic phospholipase A2 (cPLA2) in human platelets. 人血小板中Ca(2+)敏感的胞质磷脂酶A2 (cPLA2)。

Journal of lipid mediators Pub Date : 1993-03-01

R M Kramer, E F Roberts, J V Manetta, J R Sportsman, J A Jakubowski

引用次数: 0

Interfacial catalysis and production of a high ratio of leukotriene A4 to 5-HPETE by 5-lipoxygenase in a coupled assay with phospholipase A2. 5-脂氧合酶与磷脂酶A2的界面催化和高比率白三烯A4与5-HPETE的生产。

Journal of lipid mediators Pub Date : 1993-03-01

D Riendeau, J P Falgueyret, D Meisner, M M Sherman, F Laliberté, I P Street

{"title":"Interfacial catalysis and production of a high ratio of leukotriene A4 to 5-HPETE by 5-lipoxygenase in a coupled assay with phospholipase A2.","authors":"D Riendeau, J P Falgueyret, D Meisner, M M Sherman, F Laliberté, I P Street","doi":"","DOIUrl":"","url":null,"abstract":"The activity of purified 5-lipoxygenases (5-LO) shows a requirement for the presence of phosphatidylcholine or other lipids, in addition to Ca2+ and ATP. The enzymatic activity of purified human 5-lipoxygenase was dependent on the ratio of arachidonic acid to phospholipids rather than on the bulk arachidonic acid concentration, suggesting that the concentration of substrate at the lipid-water interface is important for the rate of the 5-LO reaction. Enzyme activity was also examined using vesicles of dimyristoylphosphatidylmethanol/1-palmitoyl-2-arachidonoylphosp hat idylcholine. Using PLA2 to release arachidonic acid from phospholipid, the ratio of leukotriene A4 (detected as trans-LTB4 isomers) to 5-hydroperoxyeicosatetraenoic acid (5-HPETE) accumulated depended on the 5-LO concentration and was relatively independent of the amount of PLA2. The ratio of leukotriene A4 to 5-HPETE production increased with the amount of 5-LO (1-15 micrograms/ml) to reach values (> 10) similar to those observed with ionophore-challenged human leukocytes. The data are consistent with the catalysis of 5-LO occurring at the surface of phospholipid vesicles with the 5-HPETE product being re-utilized by the LTA4 synthase reaction of 5-lipoxygenase under conditions of limiting arachidonic acid availability.","PeriodicalId":16323,"journal":{"name":"Journal of lipid mediators","volume":"6 1-3","pages":"23-30"},"PeriodicalIF":0.0,"publicationDate":"1993-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19381137","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}

引用次数: 0

14(R),15(S)-epoxyeicosatrienoic acid (14(R),15(S)-EET) receptor in guinea pig mononuclear cell membranes. 14(R)，15(S)-环氧二碳三烯酸(14(R)，15(S)-EET)受体在豚鼠单核细胞膜中的表达。

Journal of lipid mediators Pub Date : 1993-03-01

P Y Wong, K T Lin, Y T Yan, D Ahern, J Iles, S Y Shen, R K Bhatt, J R Falck

{"title":"14(R),15(S)-epoxyeicosatrienoic acid (14(R),15(S)-EET) receptor in guinea pig mononuclear cell membranes.","authors":"P Y Wong, K T Lin, Y T Yan, D Ahern, J Iles, S Y Shen, R K Bhatt, J R Falck","doi":"","DOIUrl":"","url":null,"abstract":"A high affinity binding site for 14(R),15(S)-EET, one of the major cytochrome P-450 metabolites of arachidonic acid (AA) in blood vessels, liver, kidney and urine of patients with pregnancy-induced hypertension, has been identified in a membrane preparation from guinea pig mononuclear (GPM) cells. Using a radioligand assay, binding of 14(R),15(S)-[3H]EET to its receptor site was saturable, specific and reversible. Scatchard analysis of saturation binding studies yielded a dissociation constant (Kd) of 5.7 x 10(-9) M, and maximum number of binding sites (Bmax) of 2.4 pmol/mg membrane protein. The specificity of the binding site was determined by competition studies. 14(S),15(R)-EET and 8,9-EET had a Ki of 6.3 and 8.8 nM, respectively, followed by 12(R)-HETE and LTD4. 12(S)-HETE and 5,6-EET were even less effective as a competitive inhibitor of radioligand and binding with Ki values from 2 to 20 microM. Receptor antagonists for TxA2, LTB4, LTD4 and PAF failed to displace 14(R),15(S)-[3H]EET from its binding site on GPM cell membranes. The results correlate well with the reported biological functions of 14,15-EET. In view of its potent biological activities, 14,15-EET may exert its cellular function through the binding and activation of its stereo-specific cell surface binding sites or receptor.","PeriodicalId":16323,"journal":{"name":"Journal of lipid mediators","volume":"6 1-3","pages":"199-208"},"PeriodicalIF":0.0,"publicationDate":"1993-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19381135","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}

引用次数: 0

Anti-inflammatory glucocorticoid action: inhibition of griPGHS, a new cyclooxygenase. 抗炎糖皮质激素作用:抑制新型环加氧酶griPGHS。

Journal of lipid mediators Pub Date : 1993-03-01

V D Winn, M K O'Banion, D A Young

引用次数: 0

Discovery of inhibitors of the 5-lipoxygenase activating protein (flap). 5-脂氧合酶激活蛋白(flap)抑制剂的发现。

Journal of lipid mediators Pub Date : 1993-03-01

R N Young, J W Gillard, J H Hutchinson, S Léger, P Prasit

引用次数: 0

Physiological aspects of a high affinity binding site for pancreatic-type phospholipase A2. 胰型磷脂酶A2高亲和力结合位点的生理方面。

Journal of lipid mediators Pub Date : 1993-03-01

H Arita, K Hanasaki

引用次数: 0

Amino acid residues of 5-lipoxygenase-activating protein critical for the binding of leukotriene biosynthesis inhibitors. 5-脂氧合酶激活蛋白的氨基酸残基对白三烯生物合成抑制剂的结合至关重要。

Journal of lipid mediators Pub Date : 1993-03-01

P J Vickers, M Adam, S Charleson, M Abramovitz, G O'Neill, J A Mancini

{"title":"Amino acid residues of 5-lipoxygenase-activating protein critical for the binding of leukotriene biosynthesis inhibitors.","authors":"P J Vickers, M Adam, S Charleson, M Abramovitz, G O'Neill, J A Mancini","doi":"","DOIUrl":"","url":null,"abstract":"5-Lipoxygenase-activating protein (FLAP) plays an essential role in cellular leukotriene (LT) synthesis and represents the target of three classes of LT biosynthesis inhibitors. We have taken three approaches to localize regions of FLAP involved in the binding of these inhibitors. A comparison of the amino acid sequences of FLAP from eight mammalian species identifies regions of the protein which are highly conserved and consequently may be involved in functional and inhibitor binding properties of the protein. Conversely, amino acids not conserved amongst these species are unlikely to play an essential role in inhibitor binding. Immunoprecipitation of peptide fragments of FLAP cross-linked to photoaffinity analogues of LT biosynthesis inhibitors following site-specific peptide cleavage indicates that the inhibitor attachment site is amino-terminal to 72Trp. Taken together, the cross-species analysis and photoaffinity labelling studies suggest a region within the first hydrophilic loop of FLAP which may be important for inhibitor binding. Site-directed mutagenesis of human FLAP followed by the analysis of FLAP mutants in a radioligand binding assay was used to more accurately define critical amino acid residues within this region. Mutagenesis studies reveal that mutants containing deletions of amino acids in regions of FLAP not conserved between species retain the ability to specifically bind inhibitors. Furthermore, mutants containing deletions in a highly conserved region of the protein (residues 42-61) do not bind inhibitors. These studies have therefore localized specific amino acids of FLAP which are essential for inhibitor binding. The roles that these amino acids play in inhibitor binding and may play in 5-LO activation is under investigation.","PeriodicalId":16323,"journal":{"name":"Journal of lipid mediators","volume":"6 1-3","pages":"31-42"},"PeriodicalIF":0.0,"publicationDate":"1993-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19344404","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}

引用次数: 0

Formation and effects of leukotrienes and lipoxins in human bone marrow. 白三烯和脂毒素在人骨髓中的形成和作用。

Journal of lipid mediators Pub Date : 1993-03-01

J A Lindgren, L Stenke, M Mansour, C Edenius, L Laurén, B Näsman-Glaser, I Ericsson, P Reizenstein

{"title":"Formation and effects of leukotrienes and lipoxins in human bone marrow.","authors":"J A Lindgren, L Stenke, M Mansour, C Edenius, L Laurén, B Näsman-Glaser, I Ericsson, P Reizenstein","doi":"","DOIUrl":"","url":null,"abstract":"The present results demonstrate leukotriene and lipoxin synthesis in human bone marrow and link these findings to biological effects in the same tissue. However, the mechanisms behind the described effects on myeloid progenitor cell growth are presently unknown. It is conceivable that both leukotrienes and lipoxins may act through modulation of endogenous cytokine production. However, it should be noted, that these lipoxygenase products totally failed to induce colony growth in the absence of GM-CSF. Moreover, the role of lipoxins in the bone marrow needs to be further clarified, since LXA4 induced both synergistic (with GM-CSF) and antagonistic (with LTC4) effects on progenitor cell growth. A possible pathophysiological role for leukotrienes and lipoxins may be suggested in chronic myelogenous leukemia. Thus, the capacity of hematological cells from CML patients to synthesize LTC4 was significantly increased. In addition, we have recently reported that CML platelets possessed a markedly decreased ability to participate in transcellular synthesis of the potential inhibitors of myelopoiesis, LXA4 and 5(S),12(S)-diHETE (Stenke et al., 1991b). Moreover, the production of these compounds was totally abolished in platelets obtained from CML patients in blastic crisis. Further studies should aim at defining the mechanisms behind the regulatory actions of leukotrienes and lipoxins in normal and leukemic human myelopoiesis.","PeriodicalId":16323,"journal":{"name":"Journal of lipid mediators","volume":"6 1-3","pages":"313-20"},"PeriodicalIF":0.0,"publicationDate":"1993-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19344405","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}

引用次数: 0

Diphenylmethylazine prostanoids with prostacyclin-like actions on human platelets. 对人血小板具有前列环素样作用的二苯基甲基嗪类前列腺素。

Journal of lipid mediators Pub Date : 1993-03-01

R L Jones, N H Wilson, C G Marr, G Muir, R A Armstrong

引用次数: 0

Prostaglandin endoperoxide H synthase (PGHS) activity increases with gestation and labour in human amnion. 人羊膜前列腺素内过氧化物H合成酶(PGHS)活性随妊娠和分娩而增加。

Journal of lipid mediators Pub Date : 1993-03-01

F J Teixeira, T Zakar, J Hirst, F Guo, G Machin, D M Olson

引用次数: 0