Interaction of 17α-hydroxylase, 17(20)-lyase (CYP17A1) inhibitors – abiraterone and galeterone – with human sterol 14α-demethylase (CYP51A1)

Masamrekh, Rami A.; Kuzikov, Alexey V.; Veselovsky, A. V.; Toropygin, I Iu; Shkel, Tatsiana; Strushkevich, Natallia; Gilep, Andrei A.; Usanov, Sergey A.; Archakov, Alexander I.; Shumyantseva, Victoria V.

doi:10.1016/j.jinorgbio.2018.05.010

Cited by 21 publications

(3 citation statements)

References 42 publications

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“…Most importantly, expression of SETMAR increased in leukemias, breast cancer and glioblastoma ( 37 – 39 ). CYP51A1, or lanosterol 14α-demethylase, is the essential enzyme that catalyzes an early stage of cholesterol biosynthesis and is present in all biological kingdoms ( 40 , 41 ). A study has shown that innate immune transcriptional downregulation of CYP51A1 induces lanosterol accumulation in macrophages, promoting antimicrobial activity and favoring anti-inflammatory response in macrophages ( 42 ).…”

Section: Discussionmentioning

confidence: 99%

Transcriptome Analysis of Effects of Folic Acid Supplement on Gene Expression in Liver of Broiler Chickens

Zhang

Liu

et al. 2021

Front. Vet. Sci.

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Folic acid is a water-soluble B vitamin, and plays an important role in regulating gene expression and methylation. The liver is the major site of lipid biosynthesis in the chicken. Nevertheless, how gene expression and regulatory networks are affected by folic acid in liver of broilers are poorly understood. This paper conducted the RNA-seq technology on the liver of broilers under folic acid challenge investigation. First, 405 differentially expressed genes (DEGs), including 157 significantly upregulated and 248 downregulated, were detected between the control group (C) and the 5 mg folic acid group (M). Second, 68 upregulated DEGs and 142 downregulated DEGs were determined between C group and 10 mg folic acid group (H). Third, there were 165 upregulated genes and 179 downregulated genes between M and H groups. Of these DEGs, 903 DEGs were successfully annotated in the public databases. The functional classification based on GO and KEEGG showed that “general function prediction only” represented the largest functional classes, “cell cycle” (C vs. M; M vs. H), and “neuroactive ligand-receptor interaction” (C vs. H) were the highest unique sequences among three groups. SNP analysis indicated that numbers of C, M and H groups were 145,450, 146,131, and 123,004, respectively. Total new predicted alternative splicing events in C, M, and H groups were 9,521, 9,328, and 8,929, respectively. A protein-protein interaction (PPI) network was constructed, and the top 10 hub genes were evaluated among three groups. The results of real time PCR indicated that mRNA abundance of PPARγ and FAS in abdominal fat of M and H groups were reduced compared with the C group (P < 0.05). Ultramicroscopy results showed that folic acid could reduce lipid droplets in livers from chickens. Finally, contents of LPL, PPARγ, and FAS in abdominal fat were decreased with the folic acid supplmented diets (P < 0.01). These findings reveal the effects of folic acid supplemention on gene expression in liver of broilers, which can provide information for understanding the molecular mechanisms of folic acid regulating liver lipid metabolism.

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Section: Discussionmentioning

confidence: 99%

Transcriptome Analysis of Effects of Folic Acid Supplement on Gene Expression in Liver of Broiler Chickens

Zhang

Liu

et al. 2021

Front. Vet. Sci.

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“…Meanwhile, synthesizing amino acids, nucleic acids, and tetrahydrofolic acid participates as a onecarbon unit donor and receptor [34,35]. Furthermore, FA and (6s)-5,6,7,8-tetrahydrofolate substrates could inhibit DHFR-mediated dihydrofolate reduction [36,37]. In the research of Bai et al [30], 10 mg/kg FA supplementation decreased duodenal DHFR.…”

Section: Folic Acid Absorbtion and Metabolismmentioning

confidence: 96%

Folic Acid: Sources, Chemistry, Absorption, Metabolism, Beneficial Effects on Poultry Performance and Health

Pertiwi

Mahendra

Kamaludeen

2022

Veterinary Medicine International

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Recently, there has been an increasing interest in the study of the effects of folic acid (FA) on poultry because it was observed that FA could overcome problems in poultry health while improving its performance. FA, or folate, is a water-soluble B vitamin essential in poultry, so FA intake must be available in the feed. Sources of FA in feed come from plants or animals, and animal sources have relatively more stable FA. The ingested FA will be absorbed in the intestinal lumen and transported into the liver through the blood vessels. Therefore, FA has a positive effect on the performance and health status of poultry. The effect of FA on poultry performance is to increase reproductive tract development, FA content in eggs, hatchability, weight gain, average initial body weight, feed intake, relative growth rate, chick body weight, breast fillet percentage, and reduce FCR and white striping score. At the same time, the effect on poultry health influences antioxidant activities, thyroid hormones, blood biochemicals, anti-inflammatory gene expressions, and immune responses. The present review deals with FA sources, chemistry, absorption, metabolism, effects on performance, and poultry health, which are based on valid basic information.

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“…В последнее время системные микозы, вызванные азол-резистентными штаммами патогенных грибов [3], например, Candida glabrata, получили широкое распространение среди лиц из соответствующих групп риска. В связи с этим поиск новых низкомолекулярных соединений неазольной природы (в том числе среди известных ингибиторов CYP, способных взаимодействовать с CYP51 [4]), которые бы могли ингибировать CYP51 клинических значимых грибов, представляется одним из подходов к решению этой проблемы.…”

Section: Introductionunclassified

Screening of potential non-azole inhibitors of lanosterol14-alpha demethylase (CYP51) of Candida fungi

et al. 2021

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Currently, opportunistic fungi of the genus Candida are the main causative agents of mycoses, which are especially severe upon condition of acquired immunodeficiency. The main target for the development of new antimycotics is the cytochrome P450 51 (CYP51) of the pathogenic fungus. Due to the widespread distribution of Candida strains resistancy to inhibitors of the azole class, the screening for CYP51 inhibitors both among non-azole compounds and among clinically used drugs repurposing as antimycotics is becoming urgent. To identify potential inhibitors from the non-azole group, an integrated approach was applied, including bioinformatics analysis, computer molecular modeling, and a surface plasmon resonance (SPR) technology. Using in silico modeling, the binding sites for acetylsalicylic acid, ibuprofen, chlorpromazine and haloperidol (this compounds, according to the literature, showed antimycotic activity) were predicted in the active site of CYP51 of Candida albicans and Candida glabrata. The Kd values of molecular complexes of acetylsalicylic acid, ibuprofen and haloperidol with CYP51, determined by SPR analysis, ranged from 18 μM to 126 μM. It was also shown that structural derivatives of haloperidol, containing various substituents, could be positioned in the active site of CYP51 of Candida albicans with the possible formation of coordination bonds between the hydroxyl groups of the derivatives and the iron atom in the heme of CYP51. Thus, the potential basic structures of non-azole compounds have been proposed, which can be used for the design of new CYP51 inhibitors of Candida fungi.

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Interaction of 17α-hydroxylase, 17(20)-lyase (CYP17A1) inhibitors – abiraterone and galeterone – with human sterol 14α-demethylase (CYP51A1)

Cited by 21 publications

References 42 publications

Transcriptome Analysis of Effects of Folic Acid Supplement on Gene Expression in Liver of Broiler Chickens

Transcriptome Analysis of Effects of Folic Acid Supplement on Gene Expression in Liver of Broiler Chickens

Folic Acid: Sources, Chemistry, Absorption, Metabolism, Beneficial Effects on Poultry Performance and Health

Screening of potential non-azole inhibitors of lanosterol14-alpha demethylase (CYP51) of Candida fungi

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