Effect of maleimide derivatives on superoxide-generating system of guinea-pig neutrophils stimulated by different soluble stimuli. 1984

T Yamashita, and A Someya, and Y Tsuzawa-Kido

The effect of modification of maleimide derivatives on superoxide production by guinea-pig neutrophils induced by a variety of different soluble stimuli was studied. Pretreatment of neutrophils by showdomycin, a very slowly penetrating-SH reagent, did not affect superoxide production by all of the stimuli used, suggesting no exposure of sulfhydryl groups involved in superoxide-generating system on the cell surface. Pretreatment with N-ethylmaleimide (MalNEt), a considerably penetrating-SH reagent, markedly inhibited superoxide production stimulated by formyl-methionyl-leucyl-phenylalanine (HCO-Met-Leu-Phe), cytochalasin E or digitonin, but not superoxide production stimulated by the ionophore A23187 or sodium fluoride. The oxygen consumption stimulated by HCO-Met-Leu-Phe or cytochalasin E was inhibited by MalNEt pretreatment, whereas the oxygen consumption stimulated by A23187 was not inhibited by MalNEt. The inhibition by MalNEt of superoxide production did not appear to be due to the interference with binding of the affected stimuli, since MalNEt pretreatment did not inhibit the release of lysozyme, granule enzyme, induced by HCO-Met-Leu-Phe, cytochalasin E or digitonin. Particulate fractions from MalNEt-pretreated neutrophils before exposure to the stimulus exhibited the inhibition of the enhancement of NADPH-dependent superoxide production induced by HCO-Met-Leu-Phe, cytochalasin E or digitonin, but not A23187, whereas treatment of neutrophils with MalNEt after activation by these stimuli had no effect on the NADPH oxidase activity in particulate fractions. Direct exposure of particulate fractions from A23187-stimulated neutrophils to MalNEt showed no actual susceptibility of NADPH oxidase to MalNEt inhibition. These findings suggest that the inhibitory effect of MalNEt is caused by the modification of the process of the activation by the affected stimuli of the superoxide system, probably NADPH oxidase and that at least two mechanisms exist for activation of superoxide-generating system in guinea-pig neutrophils on the basis of the susceptibility to MalNEt inhibition.

UI MeSH Term Description Entries
D008301 Maleimides Derivatives of maleimide (the structural formula H2C2(CO)2NH) containing a pyrroledione ring where the hydrogen atom of the NH group is replaced with aliphatic or aromatic groups.
D009247 NADH, NADPH Oxidoreductases A group of oxidoreductases that act on NADH or NADPH. In general, enzymes using NADH or NADPH to reduce a substrate are classified according to the reverse reaction, in which NAD+ or NADP+ is formally regarded as an acceptor. This subclass includes only those enzymes in which some other redox carrier is the acceptor. (Enzyme Nomenclature, 1992, p100) EC 1.6. Oxidoreductases, NADH, NADPH,NADPH Oxidoreductases NADH,Oxidoreductases NADH, NADPH
D009504 Neutrophils Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes. LE Cells,Leukocytes, Polymorphonuclear,Polymorphonuclear Leukocytes,Polymorphonuclear Neutrophils,Neutrophil Band Cells,Band Cell, Neutrophil,Cell, LE,LE Cell,Leukocyte, Polymorphonuclear,Neutrophil,Neutrophil Band Cell,Neutrophil, Polymorphonuclear,Polymorphonuclear Leukocyte,Polymorphonuclear Neutrophil
D010101 Oxygen Consumption The rate at which oxygen is used by a tissue; microliters of oxygen STPD used per milligram of tissue per hour; the rate at which oxygen enters the blood from alveolar gas, equal in the steady state to the consumption of oxygen by tissue metabolism throughout the body. (Stedman, 25th ed, p346) Consumption, Oxygen,Consumptions, Oxygen,Oxygen Consumptions
D002462 Cell Membrane The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells. Plasma Membrane,Cytoplasmic Membrane,Cell Membranes,Cytoplasmic Membranes,Membrane, Cell,Membrane, Cytoplasmic,Membrane, Plasma,Membranes, Cell,Membranes, Cytoplasmic,Membranes, Plasma,Plasma Membranes
D005033 Ethylmaleimide A sulfhydryl reagent that is widely used in experimental biochemical studies. N-Ethylmaleimide,N Ethylmaleimide
D006168 Guinea Pigs A common name used for the genus Cavia. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research. Cavia,Cavia porcellus,Guinea Pig,Pig, Guinea,Pigs, Guinea
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D012787 Showdomycin 3-beta-D-Ribofuranosylmaleimide. Antineoplastic antibiotic isolated from Streptomyces showdoensis. It is possibly active also as a sulfhydryl reagent.
D012995 Solubility The ability of a substance to be dissolved, i.e. to form a solution with another substance. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed) Solubilities

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