Search results for "Hydroxysteroid"
showing 10 items of 21 documents
Dihydrodiol dehydrogenase activities of rabbit liver are associated with hydroxysteroid dehydrogenases and aldo-keto reductases.
1992
1. Dihydrodiol dehydrogenase activities were investigated in rabbit liver. Using a five-step purification scheme, eight isoenzymes of dihydrodiol dehydrogenase with isoelectric points of 5.55-9.3 and promoter molecular masses of 34-35 kDa were purified to apparent homogeneity and designated CF-1 to CF-6, CM-1 and CM-2. 2. CF-1 and CF-2 had near-neutral isoelectric points of 7.4 and 6.8 and molecular masses of about 125 kDa in the native state. Both enzymes readily accepted NAD+ as well as NADP+ as coenzymes, had relatively low Km values of 0.33 mM and 0.47 mM for benzene dihydrodiol and resembled previously described carbonyl reductases in their substrate specificity towards ketones and qui…
Proteomic signature of the Dravet syndrome in the genetic Scn1a-A1783V mouse model.
2021
Abstract Background Dravet syndrome is a rare, severe pediatric epileptic encephalopathy associated with intellectual and motor disabilities. Proteomic profiling in a mouse model of Dravet syndrome can provide information about the molecular consequences of the genetic deficiency and about pathophysiological mechanisms developing during the disease course. Methods A knock-in mouse model of Dravet syndrome with Scn1a haploinsufficiency was used for whole proteome, seizure, and behavioral analysis. Hippocampal tissue was dissected from two- (prior to epilepsy manifestation) and four- (following epilepsy manifestation) week-old male mice and analyzed using LC-MS/MS with label-free quantificati…
Activation of propane 2-nitronate to a genotoxicant in V79-derived cell lines engineered for the expression of rat hepatic sulfotransferases
1999
2-Nitropropane (2-NP) is a genotoxic hepatocarcinogen in rats. The genotoxicity of the compound has been attributed to a sulfotransferase-mediated formation of DNA-reactive species from the anionic form of 2-NP, propane 2-nitronate (P2N). Several observations have suggested that sulfotransferases (SULTs) 1A1 and/or 1C1 may be important in the activation of P2N to a genotoxicant in rat liver, but a definite proof is lacking. In order to identify the sulfotransferase(s) of rat liver that are capable of activating P2N, we have investigated the genotoxicity of P2N in various V79-derived cell lines engineered for expression of individual forms of rat hepatic sulfotransferases. Genotoxicity was a…
17beta-hydroxysteroid dehydrogenase-3 deficiency: a rare endocrine cause of male-to-female sex reversal.
2006
Deficiency of 17beta-hydroxysteroid dehydrogenase type 3 (17beta-HSD3), due to mutations in the gene encoding the enzyme, results in a rare autosomal recessive form of male-to-female sex reversal. Mutated genes encode an abnormal enzyme with absent or reduced ability to convert Delta4-androstenedione to testosterone in the testis. Affected individuals are genetically males who developed internal male Wolffian structures but female external genitalia. Such individuals are usually raised as females and diagnosis is made at puberty, when they show virilization. Correct diagnosis is mandatory to optimize treatment and follow-up. In the present paper we report the clinical history, endocrine eva…
Chiral Inversion of 1-Hydroxyethylpyrene Enantiomers Mediated by Enantioselective Sulfotransferases
1998
The benzylic alcohol 1-hydroxyethylpyrene (1-HEP) is activated to a mutagen by sulfotransferases. The sulfuric acid ester formed is difficult to detect, as it is rapidly hydrolysed back to the alcohol. Incubation of the individual enantiomers of 1-HEP with human hydroxysteroid sulfotransferase (hHST) or estrogen sulfotransferase (hEST), expressed in bacteria, led to the formation of the other enantiomer. The rates of sulfation were determined from the initial rates of chiral inversion of the alcohol, knowing that hydrolysis follows an SN1 mechanism and therefore produces racemic alcohol. hEST showed high enantioselectivity for S-1-HEP, whereas hHST strongly preferred the R-enantiomer. The r…
Screening of Ovarian steroidogenic pathway in Ciona intestinalis and its modulation after Tributyltin exposure
2010
In this study, we have identified several ovarian steroids in Ciona with high similarity to vertebrate steroids and showed that cholesterol, corticosterone, dehydroepiandrosterone, estrone, estradiol-17beta, testosterone, pregnenolone, progesterone, have identical molecular spectra with vertebrate steroids. In addition, we have studied the effects of an endocrine disruptor (tributyltin: TBT) on these sex hormones and their precursors, ovarian morphology, and gene expression of some key enzymes in steroidogenic pathway in the ovary of Ciona. Ovarian specimens were cultured in vitro using different concentrations of TBT (10{sup -5}, 10{sup -4} and 10{sup -3} M). Ethanol was used as solvent co…
Stable Expression of Heterologous Sulfotransferase in V79 Cells: Activation of Primary and Secondary Benzylic Alcohols
1994
Abstract A sulfotransferase (ST) capable of activating 1-hydroxymethylpyrene (HMP) and 9-hydroxymethylanthracene (HMA) to mutagens was purified from rat liver. This enzyme appeared to be identical with hydroxysteroid STa, whose cDNA was cloned and stably expressed in Chinese hamster V79 cells. Several primary and secondary benzylic alcohols derived from polycyclic aromatic hydrocarbons induced gene mutations, sister chromatid exchanges (SCE) and/or cytotoxicity in these cells.
External Versus Internal Metabolic Activation of Polycyclic Aromatic Compounds in Mutagenicity Tests: A Comparison Using Heterologous Expression Syst…
1996
Abstract Benzo[a]pyrene-trans-7,8-dihydrodiol was virtually non-mutagenic to Chinese hamster V79p cells, but was strongly mutagenic to a V79-derived cell line expressing cytochrome P450 1A1, when the cells were exposed separately. In mixed cultures of these two cell types, it showed about 50 % of the mutagenic activity in V79p cells, compared to that observed in the enzyme-proficient cell line, indicating an efficient intercellular transfer of the active metabolite. The benzylic alcohols 1-hydroxymethylpyrene and 6-hydroxymethylbenzo[a]-pyrene were weakly mutagenic to Salmonella typhimurium TA1538 in the absence of a metabolic activation system, but were potent mutagens to a TA1538-derived …
Small molecule modulators of amine oxidation, nuclear receptor signaling and glucuronidation : 3-phenylcoumarin as a scaffold of interest
2018
The costs of the drug development process are moderated as computer-aided drug design methods are able to expedite the steps required for lead identification. In fact, computational tools are nowadays virtually indispensable from target identification and validation to preclinical tests due to exponential growth of available information regarding both potential targets and small molecules. One such small molecule with growing number of variations is coumarin. Coumarin scaffold and its various derivatives continue to interest researchers for their vast application potential. Since naturally occurring coumarins are known for example for their antioxidant and anti-inflammatory properties, thos…
16α-Iodo-3,17β-estradiol: A stable ligand for estrogen receptor determinations in tissues with high 17β-hydroxysteroid dehydrogenase activity
1983
Recently, the successful synthesis of radioiodinated 16 alpha-iodo-3,17 beta-estradiol-[125I] [125I]E2 was reported [1]. This new ligand has similar binding characteristics to the estrogen receptor (ER) [2-5] as the currently used tritium labeled estradiol [3H]E2. However, it offers several advantageous features: (a) high specific activity (theoretically 2,000 Ci/mmol) [1]; (b) minor problems with radioactive waste due to its short half life and (c) the possibility of simultaneous determination of ER and progesterone receptors (PgR) by double labeling with [125I]E2 and [3H]R5020 [6, 7]. As we are presently trying to determine ER and PgR in human placental cytosols we were interested in the …