Inhibition of the Enzymic Oxidation of DPNH by Ster Hormones

Kl, Yielding; Gm, Tomkins

doi:10.1073/pnas.45.12.1730

Cited by 42 publications

(9 citation statements)

References 21 publications

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“…Morse and Fitzgerald (13) observed inhibition of NADH oxidase and (cytochrome b) L-lactate dehydrogenase by progesterone in cell membrane preparations of N. gonorrhoeae and suggested that the steroid bound at or adjacent to membrane-bound enzymes involved in electron transport. Inhibition of electron transfer in mitochondria by progesterone has also been demonstrated in several studies (22,24,27). The results of the present study have shown conclusively that progesterone binds to the cytoplasmic membrane of N. gonorrhoeae CS-7.…”

Section: Discussionsupporting

confidence: 88%

Binding of Progesterone to Neisseria gonorrhoeae and Other Gram-Negative Bacteria

Miller

Morse

1977

Infect Immun

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The binding of [1,2-3H]progesterone to progesterone-sensitive Neisseria gonorrhoeae CS-7 and the progesterone-insensitive Neisseria mucosa, Pseudomonas aeruginosa, and Salmonella typhimurium (rough and smooth strains) was investigated. The kinetics of binding to N. gonorrhoeae CS-7 demonstrated that the majority of the progesterone binding occurred and equilibrium was reached within the first 30 min. Despite the rapid binding of progesterone, only about 20% of the added steroid was bound at the cell concentration used throughout this study. Whole cells of progesterone-insensitive bacteria bound progesterone less efficiently than the progesterone-sensitive N. gonorrhoeae CS-7. N. mucosa bound low amounts of this steroid (20% of that bound by N. gonorrhoeae CS-7) whereas the other gram-negative bacteria exhibited little progesterone binding (<3% of that bound byN. gonorrhoeae CS-7). The outer membrane permeability of N. gonorrhoeae CS-7, as measured by crystal violet uptake and inhibition, was similar to the deep rough mutant of S. typhimurium TA 1535. The latter organism neither bound nor was inhibited by progesterone. However, isolated cell envelopes ofN. gonorrhoeae and progesterone-insensitive bacteria all bound progesterone equally well. Cortisone and cholesterol, although structurally similar to progesterone, were not inhibitory to N. gonorrhoeae and did not bind to whole cells as well as progesterone. The major site of progesterone binding appeared to be the cytoplasmic membrane, which bound four times more progesterone than the outer membrane. In addition, isolated cytoplasmic membrane proteins bound more than three times more progesterone per milligram of protein than the intact membrane.

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Section: Discussionsupporting

confidence: 88%

Binding of Progesterone to Neisseria gonorrhoeae and Other Gram-Negative Bacteria

Miller

Morse

1977

Infect Immun

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“…Phagocytizing leucocytes that were treated with hydrocortisone produced less hydrogen peroxide than control preparations (Table V) (8) 0.51 4±0.06 (15) 0.57 ±0.07 (10) (6%) (12%) …”

Section: Phagocytosis Phagocytosis Was Similar In Normal Pmn and Pmnmentioning

confidence: 99%

“…Hydrocortisone has been shown to be a potent inhibitor of NADH oxidase in several other biological systems (8). Large doses were required to inhibit this enzyme in intact leukocytes.…”

Section: Phagocytosis Phagocytosis Was Similar In Normal Pmn and Pmnmentioning

confidence: 99%

The effect of an NADH oxidase inhibitor (hydrocortisone) on polymorphonuclear leukocyte bactericidal activity

Mandell¹,

Rubin²,

Hook³

1970

J. Clin. Invest.

167

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A B S T R A CT Polymorphonuclear neutrophils (PMN) from patients with chronic granulomatous disease of childhood have impaired bactericidal activity and are deficient in diphosphopyridine nucleotide, reduced form of, (NADH) oxidase. Since hydrocortisone had been shown to inhibit NADH oxidation, experiments were undertaken to determine the effect of hydrocortisone on several parameters of human PMN function.The phagocytic and bactericidal capacity of PMN with or without hydrocortisone (2.1 mM) was determined by quantitation of cell-free, cell-associated, and total bacteria. Phagocytosis of Staphylococcus autreus and several gram-negative rods was unimpaired by the presence of hydrocortisone in the media. In contrast, killing of bacteria was markedly impaired by hydrocortisone. After 30 min of incubation, there were 20-400 times as many bacteria surviving in hydrocortisone-treated PMN as in simultaneously run controls without hydrocortisone.The defect of intracellular killing noted in the presence of hydrocortisone was not related to impaired degranulation. Quantitative kinetic studies of degranulation revealed no difference in the release of granule associated acid phosphatase in hydrocortisone-treated and control PMN after phagocytosis. Electron microscopy of PMN also indicated that the presence of hydrocortisone had no effect on the extent of degranulation after phagocytosis. These observations were confirmed by studies using histochemical techniques to detect lysosomal enzymes.After phagocytosis, hydrocortisone-treated P.N demonstrated less NADH oxidase activity, oxygen consumption, and hydrogen peroxide production than postphagocytic control PMN. In addition, Nitro blue tetrazolium dye reduction was diminished in hydrocortisonetreated PMN.

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“…Estrogens have been shown to stimulate the transfer of hydrogen between di-and triphosphopyridine nucleotides,2 ' although there is disagreement as to the role of steroids in this reaction.4' Recently, steroids were found to inhibit reduced diphosphopyridine nucleotide oxidation by enzyme preparations from mammalian and microbial sources.6 I This action appears to be a general property shared by a large number of steroids. 7 This study demonstrates a highly specific inhibitory effect on mammalian glucose-6-phosphate dehydrogenase (G-6-PD) of very low concentrations of dehydroisoandrosterone, pregnenolone, and certain related steroids. These steroids are not inhibitors of yeast or spinach G-6-PD or of mammalian 6-phosphogluconic dehydrogenase or isocitric dehydrogenase.…”

mentioning

confidence: 90%

Inhibition of Mammalian Glucose-6-Phosphate Dehydrogenase by Steroids

Marks

Banks²

1960

Proc. Natl. Acad. Sci. U.S.A.

196

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It has been considered for some time that steroid hormones may exert their regulatory effects by influencing certain enzymes.' However, our present knowledge of the mechanisms of steroid action upon enzymes is limited. Estrogens have been shown to stimulate the transfer of hydrogen between di-and triphosphopyridine nucleotides,2 ' although there is disagreement as to the role of steroids in this reaction.4' Recently, steroids were found to inhibit reduced diphosphopyridine nucleotide oxidation by enzyme preparations from mammalian and microbial sources.6 I This action appears to be a general property shared by a large number of steroids.7This study demonstrates a highly specific inhibitory effect on mammalian glucose-6-phosphate dehydrogenase (G-6-PD) of very low concentrations of dehydroisoandrosterone, pregnenolone, and certain related steroids. These steroids are not inhibitors of yeast or spinach G-6-PD or of mammalian 6-phosphogluconic dehydrogenase or isocitric dehydrogenase.Materials and Methods.-Preparation of enzymes: G-6-PD was purified from human erythrocytes by a procedure described in detail elsewhere' involving ammonium sulfate fractionation followed by absorption on calcium phosphate gel, elution in a phosphate buffer, and a second series of ammonium sulfate precipitations. The final product generally had a specific activity 500-fold that of the crude hemolysate in a yield of about 40 per cent. This preparation was essentially free of hemoglobin and 6-phosphogluconic dehydrogenase activity.Crude enzyme preparations were obtained from human and rat tissues and from spinach by homogenizing freshly obtained material in isotonic potassium chloride buffered at pH 7.4 (10%, weight/volume). The homogenate was centrifuged 30 minutes at 18,000 X g to sediment debris. The supernatant fluid was employed for assays of enzyme activity.Partially purified yeast G-6-IPD and pig heart isocitric dehydrogenase were obtained from Sigma Chemical Corporation. IPartially purified 6-phosphogluconic dehydrogenase was prepared from rat liver by the method of Glock and AIcLean.9 Enzyme assays: Purified preparations of G-6-PD were assayed by the method of Kornberg and Horecker.10 In measuring G-6-PD activity in crude tissue preparations, due to the presence of 6-phosphogluconic dehydrogenase, the rate of TPNH formation exceeds the rate of glucose-6-phosphate oxidation. Accordingly, in crude preparations, G-6-PD activity was assayed by the method of Kornberg andHorecker"°determining the initial rate of TPNH formation by measuring the change of absorption at 340 m,4 with an automatic recording Cary spectrophotometer or, alternatively, by the method of Glock and AMcLean.9 In this latter method, G-6-PD activity is taken as the difference in the rate of TP'NH reduction when the reaction mixture contains both 6-phosphogluconate plus glucose-6-phosphate and in the presence of 6-phosphogluconate alone. Comparable results with 447

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Inhibition of the Enzymic Oxidation of DPNH by Ster Hormones

Cited by 42 publications

References 21 publications

Binding of Progesterone to Neisseria gonorrhoeae and Other Gram-Negative Bacteria

Binding of Progesterone to Neisseria gonorrhoeae and Other Gram-Negative Bacteria

The effect of an NADH oxidase inhibitor (hydrocortisone) on polymorphonuclear leukocyte bactericidal activity

Inhibition of Mammalian Glucose-6-Phosphate Dehydrogenase by Steroids

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