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Reduced Metabolites (reduced + metabolite)
Selected AbstractsReduced metabolites mediate neuroprotective effects of progesterone in the adult rat hippocampus.DEVELOPMENTAL NEUROBIOLOGY, Issue 9 2006The synthetic progestin medroxyprogesterone acetate (Provera) is not neuroprotective Abstract The ovarian hormone progesterone is neuroprotective in different experimental models of neurodegeneration. In the nervous system, progesterone is metabolized to 5,-dihydroprogesterone (DHP) by the enzyme 5,-reductase. DHP is subsequently reduced to 3,,5,-tetrahydroprogesterone (THP) by a reversible reaction catalyzed by the enzyme 3,-hydroxysteroid dehydrogenase. In this study we have analyzed whether progesterone metabolism is involved in the neuroprotective effect of the hormone in the hilus of the hippocampus of ovariectomized rats injected with kainic acid, an experimental model of excitotoxic cell death. Progesterone increased the levels of DHP and THP in plasma and hippocampus and prevented kainic-acid-induced neuronal loss. In contrast to progesterone, the synthetic progestin medroxyprogesterone acetate (MPA, Provera) did not increase DHP and THP levels and did not prevent kainic-acid-induced neuronal loss. The administration of the 5,-reductase inhibitor finasteride prevented the increase in the levels of DHP and THP in plasma and hippocampus as a result of progesterone administration and abolished the neuroprotective effect of progesterone. Both DHP and THP were neuroprotective against kainic acid. However, the administration of indomethacin, a 3,-hydroxysteroid dehydrogenase inhibitor, blocked the neuroprotective effect of both DHP and THP, suggesting that both metabolites are necessary for the neuroprotective effect of progesterone. In conclusion, our findings indicate that progesterone is neuroprotective against kainic acid excitotoxicity in vivo while the synthetic progestin MPA is not and suggest that progesterone metabolism to its reduced derivatives DHP and THP is necessary for the neuroprotective effect of the hormone. © 2006 Wiley Periodicals, Inc. J Neurobiol, 2006 [source] Ethanol synthesis from glycerol by Escherichia coli redox mutants expressing adhE from Leuconostoc mesenteroidesJOURNAL OF APPLIED MICROBIOLOGY, Issue 2 2010P.I. Nikel Abstract Aims:, Analysis of the physiology and metabolism of Escherichia coli arcA and creC mutants expressing a bifunctional alcohol-acetaldehyde dehydrogenase from Leuconostoc mesenteroides growing on glycerol under oxygen-restricted conditions. The effect of an ldhA mutation and different growth medium modifications was also assessed. Methods and Results:, Expression of adhE in E. coli CT1061 [arcA creC(Con)] resulted in a 1·4-fold enhancement in ethanol synthesis. Significant amounts of lactate were produced during micro-oxic cultures and strain CT1061LE, in which fermentative lactate dehydrogenase was deleted, produced up to 6·5 ± 0·3 g l,1 ethanol in 48 h. Escherichia coli CT1061LE derivatives resistant to >25 g l,1 ethanol were obtained by metabolic evolution. Pyruvate and acetaldehyde addition significantly increased both biomass and ethanol concentrations, probably by overcoming acetyl-coenzyme A (CoA) shortage. Yeast extract also promoted growth and ethanol synthesis, and this positive effect was mainly attributable to its vitamin content. Two-stage bioreactor cultures were conducted in a minimal medium containing 100 ,g l,1 calcium d -pantothenate to evaluate oxic acetyl-CoA synthesis followed by a switch into fermentative conditions. Ethanol reached 15·4 ± 0·9 g l,1 with a volumetric productivity of 0·34 ± 0·02 g l,1 h,1. Conclusions:,Escherichia coli responded to adhE over-expression by funnelling carbon and reducing equivalents into a highly reduced metabolite, ethanol. Acetyl-CoA played a key role in micro-oxic ethanol synthesis and growth. Significance and Impact of the Study:, Insight into the micro-oxic metabolism of E. coli growing on glycerol is essential for the development of efficient industrial processes for reduced biochemicals production from this substrate, with special relevance to biofuels synthesis. [source] Stable maintenance of 5, -reductase activity in long-term subcultures of fibroblasts derived from the foreskinINTERNATIONAL JOURNAL OF UROLOGY, Issue 6 2002Kazumi Nakae Abstract Background: There is up to a 50-fold variation in control subjects in current assays of 5,-reductase activity which makes interpretation difficult. It was therefore attempted in this study to establish an assay method which produced stable 5,-reductase activity in long-term subcultured foreskin fibroblasts. Methods: Foreskin fibroblasts were obtained from three boys with phimosis (control subjects), three patients with Reifenstein syndrome and one patient with 5,-reductase deficiency (due to mutation L113P in exon 2 of the SRD5A2 gene). To maximize the number of cells in the DNA synthesis phase, cells were subcultured consistently to approximately 70% confluency. Thawed cells, frozen after the third subculture, were incubated for 24 h with [1,,2,- 3H] testosterone. 5,-Reductase activity was expressed as the sum of formed [3H] 5,-reduced metabolites (separated by thin-layer chromatography). Results: The full range of 5,-reductase activity in controls and patients with Reifenstein syndrome was 3.44,15.59 pmol/h per mg protein: a 4.53-fold variation. The activity in the patient with 5,- reductase deficiency was 0.52 pmol/h per mg protein. Conclusion: By the cell culture methods used in this study, which aimed to increase the number of cells in the DNA synthesis phase, foreskin fibroblasts maintained a considerably stable level of 5,-reductase activity during long-term subculture. Therefore, this assay method can be used for differential diagnosis of 5,-reductase deficiency from other relevant entities. [source] Sex-dimorphic effects of progesterone and its reduced metabolites on gene expression of myelin proteins by rat Schwann cellsJOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 2 2006Valerio Magnaghi Abstract Data obtained in our and other laboratories have indicated that progesterone (P) and its derivatives, dihydroprogesterone (DHP) and tetrahydroprogesterone (THP), stimulate the expression of two myelin proteins of the peripheral nervous system (PNS) [i.e., glycoprotein zero (P0) and peripheral myelin protein 22 (PMP22)]. We have now considered the effects of P and its derivatives on these and other myelin proteins [i.e., myelin-associated glycoprotein (MAG) and myelin and lymphocyte protein (MAL)] in sex-specific cultures of rat Schwann cells. Gene expression of myelin proteins was assessed by RNase protection assay. Treatment with P or DHP induced a stimulatory effect on P0 mRNA levels in male but not in female Schwann cells. In contrast, treatment with THP increased gene expression of P0 exclusively in female Schwann cells. A similar sex-difference was also evident for other myelin proteins. Indeed, PMP22 expression was stimulated by treatment with P in male cultures, whereas THP induced an increase of mRNA levels in female cultures. Moreover, MAG was stimulated by THP treatment in male cultures only, whereas MAL expression was unaffected by neuroactive steroid treatment in both male and female cultures. In conclusion, the present observations indicate that the effects of neuroactive steroids on myelin proteins are sexually dimorphic. This finding might represent an important background for sex-specific therapies of acquired and inherited peripheral neuropathies. [source] | |||||||||||||