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167 results on '"2,5-hexanedione"'

151. Role of N-acetylcysteine in protecting against 2,5-hexanedione neurotoxicity in a rat model: changes in urinary pyrroles levels and motor activity performance.

Author

Torres ME, dos Santos AP, Gonçalves LL, Andrade V, Batoréu MC, and Mateus ML

Subjects
Acetylcysteine pharmacology, Animals, Chromatography, Liquid, Hexanones toxicity, Hexanones urine, Male, Neuroprotective Agents pharmacology, Neurotoxins toxicity, Neurotoxins urine, Norleucine urine, Rats, Rats, Wistar, Tandem Mass Spectrometry, Acetylcysteine administration & dosage, Hexanones administration & dosage, Motor Activity drug effects, Neuroprotective Agents administration & dosage, Neurotoxins administration & dosage, Pyrroles urine
Abstract

The interference of N-acetylcysteine (NAC) on 2,5-hexanedione (2,5-HD) neurotoxicity was evaluated through behavioral assays and the analysis of urinary 2,5-HD, dimethylpyrrole norleucine (DMPN), and cysteine-pyrrole conjugate (DMPN NAC), by ESI-LC-MS/MS, in rats exposed to 2,5-HD and co-exposed to 2,5-HD and NAC. Wistar rats were treated with 4 doses of: 400mg 2,5-HD/kg bw (group I), 400mg 2,5-HD/kg bw+200mg NAC/kg bw (group II), 200mg NAC/kg bw (group III) and with saline (group IV). The results show a significant decrease (p<0.01) in urinary DMPN and free 2,5-HD, a significant increase (p<0.01) in DMPN NAC excretion, and a significant recovery (p<0.01) on motor activity in rats co-exposed to 2,5-HD+NAC, as compared with rats exposed to 2,5-HD alone. Taken together, our findings suggest that at the studied conditions NAC protects against 2,5-HD neurotoxicity and DMPN may be proposed as a new sensitive and specific biomarker of 2,5-HD neurotoxicity in animals treated with a toxic amount of 2,5-hexanedione., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Published
2014
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165. Engineering cofactor preference of ketone reducing biocatalysts: A mutagenesis study on a γ-diketone reductase from the yeast Saccharomyces cerevisiae serving as an example.

Author

Katzberg M, Skorupa-Parachin N, Gorwa-Grauslund MF, and Bertau M

Subjects
Alcohol Oxidoreductases chemistry, Alcohol Oxidoreductases genetics, Amino Acid Sequence, Binding Sites, Biocatalysis, Catalytic Domain, Genetic Engineering, Hexanones chemistry, Hexanones metabolism, Hydrogen Bonding, Kinetics, Molecular Sequence Data, Mutagenesis, Site-Directed, NADP metabolism, Oxidation-Reduction, Oxidoreductases chemistry, Oxidoreductases genetics, Oxidoreductases metabolism, Protein Binding, Saccharomyces cerevisiae Proteins chemistry, Saccharomyces cerevisiae Proteins genetics, Saccharomyces cerevisiae Proteins metabolism, Sequence Alignment, Sequence Homology, Amino Acid, Stereoisomerism, Alcohol Oxidoreductases metabolism, Ketones chemistry, Saccharomyces cerevisiae enzymology
Abstract

The synthesis of pharmaceuticals and catalysts more and more relies on enantiopure chiral building blocks. These can be produced in an environmentally benign and efficient way via bioreduction of prochiral ketones catalyzed by dehydrogenases. A productive source of these biocatalysts is the yeast Saccharomyces cerevisiae, whose genome also encodes a reductase catalyzing the sequential reduction of the gamma-diketone 2,5-hexanedione furnishing the diol (2S,5S)-hexanediol and the gamma-hydroxyketone (5S)-hydroxy-2-hexanone in high enantio- as well as diastereoselectivity (ee and de >99.5%). This enzyme prefers NADPH as the hydrogen donating cofactor. As NADH is more stable and cheaper than NADPH it would be more effective if NADH could be used in cell-free bioreduction systems. To achieve this, the cofactor binding site of the dehydrogenase was altered by site-directed mutagenesis. The results show that the rational approach based on a homology model of the enzyme allowed us to generate a mutant enzyme having a relaxed cofactor preference and thus is able to use both NADPH and NADH. Results obtained from other mutants are discussed and point towards the limits of rationally designed mutants.

Published
2010
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166. Experimental increase of neurofilament transport rate: decreases in neurofilament number and in axon diameter

Author

Michael J. Katz, Pierluigi Gambetti, Raymond J. Lasek, Salvatore Monaco, and Lucila Autilio-Gambetti

Subjects
Axonal neuropathy, Male, Neurofilament, Intermediate Filaments, Microtubules, Pathology and Forensic Medicine, Cellular and Molecular Neuroscience, Drug treatment, chemistry.chemical_compound, Microtubule, medicine, Hexane-2,5-dione, Animals, Nearest-neighbor distance, Axon, Cytoskeleton, Giant axonal neuropathy, Axonal transport, Morphometry, Neurofilaments, 5-Hexanedione, Biological Transport, Optic Nerve, Rats, Inbred Strains, General Medicine, medicine.disease, 2,5-Hexanedione, Axonal caliber, Axons, Rats, Hexanones, Microscopy, Electron, medicine.anatomical_structure, nervous system, Neurology, chemistry, Biophysics, Axoplasmic transport, Neurology (clinical), Neuroscience
Abstract

In 2,5-hexanedione (2,5-HD)-induced axonal neuropathy, the rate of neurofilament (NF) transport increases in optic axons. To test the prediction that increases in the rate of polymer transport in any one locality of the axon lead directly to a decrease in the number of NF in that locality, NF and microtubules (MT) were quantitatively analyzed in axonal cross sections. In 2,5-HD axons the number of NF was 38% of that in control axons while the number of MT was not significantly changed; it appears that the drug treatment decreases NF number in the proximal axon regions, most directly through an increase in rate of NF transport. In those regions, the cross-sectional areas of the 2,5-HD-treated axons were 45% smaller than those of control axons; although the axons had shrunk in diameter, they retained their normal cylindrical shapes as measured by the index of circularity. Reduced internal expansive forces in the axon, working in conjunction with the normal external compressive forces, appear to reduce the radius of the axon. Quantitative analyses demonstrated that the average and the maximum lateral spacings between NF-NF, NF-MT, and MT-MT were all 30% larger in 2,5-HD-treated axons than in control axons. This suggests that polymers are relatively free to move laterally away from one another and to fill the available, space within the axon. These observations are not consistent with models wherein 2,5-HD acts to crosslink the NF into an immobile network that can no longer advance within the axon. Instead, it appears more likely that 2,5-HD acts selectively on the interaction between some NF and the slow transport mechanism to increase the rate of NF transport.

Published
1989

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