Reactive oxygen species induce cellular damage and have been implicated as mediators for cellular signaling pathways. However, a linkage between the cellular redox status and cell cycle progression has not been demonstrated. We previously demonstrated, using the Chinese hamster ovary cell line AS52, that the cytotoxic and mutagenic effects of oxidative stress is prevented by ascorbic acid (AA), but only when cells are treated with AA prior to treatment with the stressor. To elucidate the mechanism(s) responsible for this effect, we determined the effect of AA on cell cycle progression during oxidative stress. Flow cytometric analyses demonstrated that treatment of AS52 cells with AA (50 microM), prior to treatment with a radical generating system (RGS), enhanced cell cycle arrest at the G2/M DNA damage checkpoint when compared to cells treated with RGS. AA had no effect on cell cycle progression in the absence of oxidative stress. Furthermore, under conditions that prevent the reduction of dehydroascorbate (DHA), the oxidized form of AA, cell cycle arrest was also induced at the G2/M DNA damage checkpoint. These observations demonstrate that during periods of oxidative stress, AA functions as an antioxidant and DHA enhances transient arrest at the G2/M checkpoint by delaying the activation of cyclin B-cdc2. These results suggest the presence of a unique redox mechanism for the regulation of cell cycle progression and also demonstrate a novel mechanism by which AA protects cells from damage due to oxidative stress.

Animals↗

PubMed1997

Effectiveness of digitalis with or without acebutolol in preventing atrial arrhythmias after coronary artery surgery.

In this study, a beta-adrenergic blocker in combination with digoxin provided marginal protection against atrial fibrillation/flutter after coronary artery surgery. The economic comparison of patients who did and did not develop atrial fibrillation/flutter indicates that prevention of these arrhythmias can have a significant impact on length of hospital stay and cost of this common surgical procedure.

Acebutolol↗

PubMed1994

Domain structure of Escherichia coli DNA gyrase as revealed by differential scanning calorimetry.

The domain structure of DNA gyrase from Escherichia coli has been examined using differential scanning microcalorimetry. The intact enzyme (an A2B2 tetramer) shows at least four transitions with apparent Tm's at 44.8, 53.3, 58.6, and 60.7 degrees C. Comparison with the thermal stabilities of the two separate subunits and genetically-engineered protein fragments has been used to assign these transitions to individual domains within the intact gyrase proteins. The thermal unfolding of DNA gyrase and all individual fragments are irreversible under the conditions of the calorimetric experiment. Further evidence for the assignment of transitions to particular domains has been obtained by studying the effects of tight-binding ligands such as novobiocin on the thermal stabilities of the various protein fragments.

Adenosine Triphosphate↗

PubMed1991

Limitations of testing methods for evaluation of dual chamber versus single chamber adaptive rate pacing.

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Aged↗

PubMed1987

Biosynthetic studies on antibiotic A47934.

A47934, a peptide antibiotic produced by Streptomyces toyocaensis, belongs to the glycopeptide class of compounds which includes ristocetin and vancomycin. Incorporation studies with radioisotope-labeled substrates indicated that tyrosine, p-hydroxyphenylglycine, p-hydroxyphenylglyoxylate, acetate, and sulfate were efficiently incorporated into A47934. This is consistent with the reported biosynthesis of other glycopeptide antibiotics. Prototrophic mutants blocked in antibiotic biosynthesis were isolated at a low frequency (0.4%) after mutagenesis. Secretor-convertor pairings of the 36 mutants obtained demonstrated that they belonged to three classes: two groups of secretor-convertor pairs and a larger group of mutants that did not make antibiotic under any condition tested. Neither the secretor-convertor studies not supplementation of the cultures with putative biosynthetic intermediates was useful in identifying the location of the biosynthetic blocks. All studies to determine the timing of the sulfate addition step in the biosynthesis indicated that the sulfate is added prior to the formation of intermediates that possess antimicrobial activity.

Anti-Bacterial Agents↗