Effect of mitomycin C on prostacyclin synthesis by human endothelial cells. 1988

A Duperray, and L Tranqui, and J L Alix, and D Cordonnier
INSERM U.217, DRF/LBio/Laboratoire d'Hématologie CEN.G, Grenoble, France.

The effect of mitomycin C (MMC) on the biosynthesis of prostacyclin was tested in culture of human umbilical cord vein endothelial cells. A 30% inhibition of the thrombin-stimulated prostacyclin synthesis by MMC was observed at concentrations of the same order as those found in MMC-treated patients (3 micrograms/ml as compared with the peak plasma concentration varying between 0.4 and 3.2 micrograms/ml (J. Den Hartigh et al., Cancer Res 40:5017-5021, 1983)). This inhibition was found for incubation times ranging from 15 to 30 min during which the cell viability was unaltered. Under these conditions it was found that the release of von Willebrand factor by the endothelial cell was unaffected. Since MMC toxicity in man is expressed by a chronic haemolytic and uraemic syndrome, the inhibitory capacity of MMC on prostacyclin synthesis favours the hypothesis that a deficiency in prostacyclin synthesis leads to the development of this syndrome in man.

UI MeSH Term Description Entries
D008937 Mitomycins A group of methylazirinopyrroloindolediones obtained from certain Streptomyces strains. They are very toxic antibiotics used as ANTINEOPLASTIC AGENTS in some solid tumors. PORFIROMYCIN and MITOMYCIN are the most useful members of the group.
D011464 Epoprostenol A prostaglandin that is a powerful vasodilator and inhibits platelet aggregation. It is biosynthesized enzymatically from PROSTAGLANDIN ENDOPEROXIDES in human vascular tissue. The sodium salt has been also used to treat primary pulmonary hypertension (HYPERTENSION, PULMONARY). Prostacyclin,Prostaglandin I2,Epoprostanol,Epoprostenol Sodium,Epoprostenol Sodium Salt, (5Z,9alpha,11alpha,13E,15S)-Isomer,Flolan,Prostaglandin I(2),Veletri
D004730 Endothelium, Vascular Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components. Capillary Endothelium,Vascular Endothelium,Capillary Endotheliums,Endothelium, Capillary,Endotheliums, Capillary,Endotheliums, Vascular,Vascular Endotheliums
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000001 Calcimycin An ionophorous, polyether antibiotic from Streptomyces chartreusensis. It binds and transports CALCIUM and other divalent cations across membranes and uncouples oxidative phosphorylation while inhibiting ATPase of rat liver mitochondria. The substance is used mostly as a biochemical tool to study the role of divalent cations in various biological systems. 4-Benzoxazolecarboxylic acid, 5-(methylamino)-2-((3,9,11-trimethyl-8-(1-methyl-2-oxo-2-(1H-pyrrol-2-yl)ethyl)-1,7-dioxaspiro(5.5)undec-2-yl)methyl)-, (6S-(6alpha(2S*,3S*),8beta(R*),9beta,11alpha))-,A-23187,A23187,Antibiotic A23187,A 23187,A23187, Antibiotic
D001241 Aspirin The prototypical analgesic used in the treatment of mild to moderate pain. It has anti-inflammatory and antipyretic properties and acts as an inhibitor of cyclooxygenase which results in the inhibition of the biosynthesis of prostaglandins. Aspirin also inhibits platelet aggregation and is used in the prevention of arterial and venous thrombosis. (From Martindale, The Extra Pharmacopoeia, 30th ed, p5) Acetylsalicylic Acid,2-(Acetyloxy)benzoic Acid,Acetysal,Acylpyrin,Aloxiprimum,Colfarit,Dispril,Easprin,Ecotrin,Endosprin,Magnecyl,Micristin,Polopirin,Polopiryna,Solprin,Solupsan,Zorprin,Acid, Acetylsalicylic
D013917 Thrombin An enzyme formed from PROTHROMBIN that converts FIBRINOGEN to FIBRIN. Thrombase,Thrombin JMI,Thrombin-JMI,Thrombinar,Thrombostat,alpha-Thrombin,beta,gamma-Thrombin,beta-Thrombin,gamma-Thrombin,JMI, Thrombin
D014841 von Willebrand Factor A high-molecular-weight plasma protein, produced by endothelial cells and megakaryocytes, that is part of the factor VIII/von Willebrand factor complex. The von Willebrand factor has receptors for collagen, platelets, and ristocetin activity as well as the immunologically distinct antigenic determinants. It functions in adhesion of platelets to collagen and hemostatic plug formation. The prolonged bleeding time in VON WILLEBRAND DISEASES is due to the deficiency of this factor. Factor VIII-Related Antigen,Factor VIIIR-Ag,Factor VIIIR-RCo,Plasma Factor VIII Complex,Ristocetin Cofactor,Ristocetin-Willebrand Factor,von Willebrand Protein,Factor VIII Related Antigen,Factor VIIIR Ag,Factor VIIIR RCo,Ristocetin Willebrand Factor
D015121 6-Ketoprostaglandin F1 alpha The physiologically active and stable hydrolysis product of EPOPROSTENOL. Found in nearly all mammalian tissue. 6-Keto-PGF1 alpha,6-Oxo-PGF1 alpha,6-Oxoprostaglandin F1 alpha,6 Ketoprostaglandin F1 alpha,6 Keto PGF1 alpha,6 Oxo PGF1 alpha,6 Oxoprostaglandin F1 alpha,F1 alpha, 6-Ketoprostaglandin,F1 alpha, 6-Oxoprostaglandin,alpha, 6-Keto-PGF1,alpha, 6-Ketoprostaglandin F1,alpha, 6-Oxo-PGF1,alpha, 6-Oxoprostaglandin F1
D016685 Mitomycin An antineoplastic antibiotic produced by Streptomyces caespitosus. It is one of the bi- or tri-functional ALKYLATING AGENTS causing cross-linking of DNA and inhibition of DNA synthesis. Mitomycin C,Ametycine,Mitocin-C,Mitomycin-C,Mutamycin,NSC-26980,Mitocin C,MitocinC,NSC 26980,NSC26980

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