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https://www.readbyqxmd.com/read/28336949/induction-of-apoptosis-and-ganoderic-acid-biosynthesis-by-camp-signaling-in-ganoderma-lucidum
#1
Bang-Jau You, Ni Tien, Miin-Huey Lee, Bo-Ying Bao, Yih-Shyuan Wu, Tsung-Chi Hu, Hong-Zin Lee
Apoptosis is an essential physiological process that controls many important biological functions. However, apoptosis signaling in relation to secondary metabolite biosynthesis in plants and fungi remains a mystery. The fungus Ganoderma lucidum is a popular herbal medicine worldwide, but the biosynthetic regulation of its active ingredients (ganoderic acids, GAs) is poorly understood. We investigated the role of 3',5'-cyclic adenosine monophosphate (cAMP) signaling in fungal apoptosis and GA biosynthesis in G...
March 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28322148/effects-of-exogenous-salicylic-acid-on-ganoderic-acid-biosynthesis-and-the-expression-of-key-genes-in-the-ganoderic-acid-biosynthesis-pathway-in-the-lingzhi-or-reishi-medicinal-mushroom-ganoderma-lucidum-agaricomycetes
#2
Peng-Fei Cao, Chen-Gao Wu, Zhi-Hao Dang, Liang Shi, Ai-Liang Jiang, Ang Ren, Ming-Wen Zhao
We demonstrate herein that salicylic acid (SA) can enhance ganoderic acid (GA) accumulation in the lingzhi or reishi medicinal mushroom Ganoderma lucidum. Following treatment with different concentrations of SA, the GA content was increased 22.72% to 43.04% compared with the control group. When the fungi were treated with 200 μmol/L SA at different times, the GA content was improved 10.21% to 35.24% compared with the control group. By choosing the optimum point based on response surface methodology, the GA content could be increased up to 229...
2017: International Journal of Medicinal Mushrooms
https://www.readbyqxmd.com/read/28314390/oxysterols-in-cosmetics-determination-by-planar-solid-phase-extraction-and-gas-chromatography-mass-spectrometry
#3
S Schrack, C Hohl, W Schwack
Sterol oxidation products (SOPs) are linked to several toxicological effects. Therefore, investigation of potential dietary uptake sources particularly food of animal origin has been a key issue for these compounds. For the simultaneous determination of oxysterols from cholesterol, phytosterols, dihydrolanosterol and lanosterol in complex cosmetic matrices, planar solid phase extraction (pSPE) was applied as clean-up tool. SOPs were first separated from more non-polar and polar matrix constituents by normal phase thin-layer chromatography and then focussed into one target zone...
November 18, 2016: Journal of Chromatography. A
https://www.readbyqxmd.com/read/28303159/antifungal-activity-of-the-ethanol-extract-from-flos-rosae-chinensis-with-activity-against-fluconazole-resistant-clinical-candida
#4
Lulu Zhang, Hui Lin, Wei Liu, Baodi Dai, Lan Yan, YongBing Cao, Yuan-Ying Jiang
This study was designed to investigate the antifungal activity of a hydroalcoholic extract from Flos Rosae Chinensis (FRC) combined with fluconazole (FCZ) against clinical isolates of Candida albicans resistant to FCZ. The minimum inhibitory concentration (MIC) of FRC was determined using a checkerboard microdilution assay. The synergistic effects of the combination of FRC and FCZ against clinical isolates of C. albicans resistant to FCZ were further confirmed by constructing time-growth curves and performing an agar diffusion test...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28294269/%C3%AE-amyrin-biosynthesis-catalytic-mechanism-and-substrate-recognition
#5
REVIEW
Tsutomu Hoshino
The enzymatic polycyclization reactions catalyzed by oxidosqualene (OXSQ) cyclases (OSCs) proceed with complete regio- and stereospecificity, leading to the formation of new C-C bonds and chiral centers and to the generation of diverse polycyclic sterols and triterpenoids. The diverse structural array is remarkable, and approximately 150 different carbon frameworks have been found. Detailed investigations on squalene-hopene cyclase (SHC) and lanosterol synthase (LaS) have been reported, but progress in the study of β-amyrin synthase, which is ubiquitously found in plants, has lagged in comparison...
March 15, 2017: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/28264842/contributions-of-both-atp-binding-cassette-transporter-and-cyp51a-proteins-are-essential-for-azole-resistance-in-aspergillus-fumigatus
#6
Sanjoy Paul, Daniel Diekema, W Scott Moye-Rowley
While azole drugs targeting the biosynthesis of ergosterol are effective antifungal agents, their extensive use has led to the development of resistant organisms. Infections involving azole resistant forms of the filamentous fungus Aspergillus fumigatus are often associated with genetic changes in the cyp51A gene encoding the lanosterol α14 demethylase target enzyme. Both a sequence duplication in the cyp51A promoter (TR34) as well as a substitution mutation in the coding sequence (L98H) are required for full expression of azole resistance...
March 6, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28258022/probes-for-protein-adduction-in-cholesterol-biosynthesis-disorders-alkynyl-lanosterol-as-a-viable-sterol-precursor
#7
Keri A Tallman, Hye-Young H Kim, Zeljka Korade, Thiago C Genaro-Mattos, Phillip A Wages, Wei Liu, Ned A Porter
The formation of lipid electrophile-protein adducts is associated with many disorders that involve perturbations of cellular redox status. The identities of adducted proteins and the effects of adduction on protein function are mostly unknown and an increased understanding of these factors may help to define the pathogenesis of various human disorders involving oxidative stress. 7-Dehydrocholesterol (7-DHC), the immediate biosynthetic precursor to cholesterol, is highly oxidizable and gives electrophilic oxysterols that adduct proteins readily, a sequence of events proposed to occur in Smith-Lemli-Opitz syndrome (SLOS), a human disorder resulting from an error in cholesterol biosynthesis...
February 24, 2017: Redox Biology
https://www.readbyqxmd.com/read/28250360/a-new-amino-acid-substitution-at-g150s-in-lanosterol-14-%C3%AE-demethylase-erg11-protein-in-multi-azole-resistant-trichosporon-asahii
#8
Hisako Kushima, Issei Tokimatsu, Hiroshi Ishii, Rie Kawano, Kentaro Watanabe, Jun-Ichi Kadota
The mechanisms of azole resistance in Trichosporon asahii have not yet been fully clarified. We previously showed that T. asahii has the ERG11 gene, coding lanosterol 14-α-demethylase (Erg11 protein; Erg11p), which is the primary target of azoles. A single amino acid substitution at G453R in Erg11p was found to induce changes in the affinity of this enzyme for azoles, especially fluconazole, in vitro. In the present study, we investigated the DNA sequences of the ERG11 gene using six different strains of clinically isolated T...
2017: Medical Mycology Journal
https://www.readbyqxmd.com/read/28242548/new-azole-derivatives-showing-antimicrobial-effects-and-their-mechanism-of-antifungal-activity-by-molecular-modeling-studies
#9
İnci Selin Doğan, Selma Saraç, Suat Sari, Didem Kart, Şebnem Eşsiz Gökhan, İmran Vural, Sevim Dalkara
Azole antifungals are potent inhibitors of fungal lanosterol 14α demethylase (CYP51) and have been used for eradication of systemic candidiasis clinically. Herein we report the design, synthesis, and biological evaluation of a series of 1-phenyl/1-(4-chlorophenyl)-2-(1H-imidazol-1-yl)ethanol esters. Many of these derivatives showed fungal growth inhibition at very low concentrations. Minimal inhibition concentration (MIC) value of 15 was 0.125 μg/mL against Candida albicans. Additionally, some of our compounds, such as 19 (MIC: 0...
April 21, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28224386/%C3%AE-bisabolol-inhibits-aspergillus-fumigatus-af239-growth-via-affecting-microsomal-%C3%A2-24-sterol-methyltransferase-as-a-crucial-enzyme-in-ergosterol-biosynthesis-pathway
#10
Zahra Jahanshiri, Masoomeh Shams-Ghahfarokhi, Farnoush Asghari-Paskiabi, Reza Saghiri, Mehdi Razzaghi-Abyaneh
Finding new compounds with antifungal properties is an important task due to the side effects of common antifungal drugs and emerging antifungal resistance in fungal strains. ∆(24)-sterol methyltransferase (24-SMT) is a crucial enzyme that plays important roles in fungal ergosterol biosynthesis pathway and is not found in humans. In the present study, the effects of α-bisabolol on Aspergillus fumigatus Af239 growth and ergosterol synthesis on the base of 24-SMT enzyme activity were studied; in addition, the expression of erg6, the gene encoded 24-SMT, was considered...
March 2017: World Journal of Microbiology & Biotechnology
https://www.readbyqxmd.com/read/28202290/effect-of-psychotropic-drug-treatment-on-sterol-metabolism
#11
Željka Korade, Wei Liu, Emily B Warren, Kristan Armstrong, Ned A Porter, Christine Konradi
Cholesterol metabolism is vital for brain function. Previous work in cultured cells has shown that a number of psychotropic drugs inhibit the activity of 7-dehydrocholesterol reductase (DHCR7), an enzyme that catalyzes the final steps in cholesterol biosynthesis. This leads to the accumulation of 7-dehydrocholesterol (7DHC), a molecule that gives rise to oxysterols, vitamin D, and atypical neurosteroids. We examined levels of cholesterol and the cholesterol precursors desmosterol, lanosterol, 7DHC and its isomer 8-dehydrocholesterol (8DHC), in blood samples of 123 psychiatric patients on various antipsychotic and antidepressant drugs, and 85 healthy controls, to see if the observations in cell lines hold true for patients as well...
February 12, 2017: Schizophrenia Research
https://www.readbyqxmd.com/read/28106743/design-synthesis-and-antifungal-activity-evaluation-of-new-thiazolin-4-ones-as-potential-lanosterol-14%C3%AE-demethylase-inhibitors
#12
Anca Stana, Dan C Vodnar, Radu Tamaian, Adrian Pîrnău, Laurian Vlase, Ioana Ionuț, Ovidiu Oniga, Brînduşa Tiperciuc
Twenty-three thiazolin-4-ones were synthesized starting from phenylthioamide or thiourea derivatives by condensation with α-monochloroacetic acid or ethyl α-bromoacetate, followed by substitution in position 5 with various arylidene moieties. All the synthesized compounds were physico-chemically characterized and the IR (infrared spectra), ¹H NMR (proton nuclear magnetic resonance), (13)C NMR (carbon nuclear magnetic resonance) and MS (mass spectrometry) data were consistent with the assigned structures...
January 17, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28102469/lanosterol-suppresses-the-aggregation-and-cytotoxicity-of-misfolded-proteins-linked-with-neurodegenerative-diseases
#13
Arun Upadhyay, Ayeman Amanullah, Ribhav Mishra, Amit Kumar, Amit Mishra
Accumulation of misfolded or aberrant proteins in neuronal cells is linked with neurodegeneration and other pathologies. Which molecular mechanisms fail and cause inappropriate folding of proteins and what is their relationship to cellular toxicity is not well known. How does it happen and what are the probable therapeutic or molecular approaches to counter them are also not clear. Here, we demonstrate that treatment of lanosterol diminishes aberrant proteotoxic aggregation and mitigates their cytotoxicity via induced expression of co-chaperone CHIP and elevated autophagy...
January 19, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28101253/2-chromon-3-yl-imidazole-derivatives-as-potential-antimicrobial-agents-synthesis-biological-evaluation-and-molecular-docking-studies
#14
Shweta Sharma, Vishal Sharma, Gurpreet Singh, Harpreet Kaur, Shubham Srivastava, Mohan Paul S Ishar
A series of novel 2-(chromon-3-yl)-4,5-diphenyl-1H-imidazoles (4a-h) were synthesized by one pot condensation of substituted 3-formylchromones (1a-h), benzil (2) and ammonium acetate (3) in refluxing acetic acid at 110 °C under N2 atmosphere. Allylation of compounds 4a-h with allyl bromide in the presence of fused K2CO3 furnished N-allyl-2-(chromon-3-yl)-4,5-diphenyl-1H-imidazoles (6a-h). The synthesized compounds were characterized spectroscopically and evaluated for in vitro antimicrobial activity against various pathogenic bacterial and fungal strains by disc diffusion method...
January 2017: Journal of Chemical Biology
https://www.readbyqxmd.com/read/28098217/disrupting-hepatocyte-cyp51-from-cholesterol-synthesis-leads-to-progressive-liver-injury-in-the-developing-mouse-and-decreases-rorc-signalling
#15
Žiga Urlep, Gregor Lorbek, Martina Perše, Jera Jeruc, Peter Juvan, Madlen Matz-Soja, Rolf Gebhardt, Ingemar Björkhem, Jason A Hall, Richard Bonneau, Dan R Littman, Damjana Rozman
Development of mice with hepatocyte knockout of lanosterol 14α-demethylase (H(Cyp51-/-)) from cholesterol synthesis is characterized by the progressive onset of liver injury with ductular reaction and fibrosis. These changes begin during puberty and are generally more aggravated in the knockout females. However, a subgroup of (pre)pubertal knockout mice (runts) exhibits a pronounced male prevalent liver dysfunction characterized by downregulated amino acid metabolism and elevated Casp12. RORC transcriptional activity is diminished in livers of all runt mice, in correlation with the depletion of potential RORC ligands subsequent to CYP51 disruption...
January 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28028245/synthesis-of-arborane-triterpenols-by-a-bacterial-oxidosqualene-cyclase
#16
Amy B Banta, Jeremy H Wei, Clare C C Gill, José-Luis Giner, Paula V Welander
Cyclic triterpenoids are a broad class of polycyclic lipids produced by bacteria and eukaryotes. They are biologically relevant for their roles in cellular physiology, including membrane structure and function, and biochemically relevant for their exquisite enzymatic cyclization mechanism. Cyclic triterpenoids are also geobiologically significant as they are readily preserved in sediments and are used as biomarkers for ancient life throughout Earth's history. Isoarborinol is one such triterpenoid whose only known biological sources are certain angiosperms and whose diagenetic derivatives (arboranes) are often used as indicators of terrestrial input into aquatic environments...
January 10, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27977118/rapid-chagas-disease-drug-target-discovery-using-directed-evolution-in-drug-sensitive-yeast
#17
Sabine Ottilie, Gregory M Goldgof, Claudia Magalhaes Calvet, Gareth K Jennings, Greg LaMonte, Jake Schenken, Edgar Vigil, Prianka Kumar, Laura-Isobel McCall, Eduardo Soares Constantino Lopes, Felicia Gunawan, Jennifer Yang, Yo Suzuki, Jair L Siqueira-Neto, James H McKerrow, Rommie E Amaro, Larissa M Podust, Jacob D Durrant, Elizabeth A Winzeler
Recent advances in cell-based, high-throughput phenotypic screening have identified new chemical compounds that are active against eukaryotic pathogens. A challenge to their future development lies in identifying these compounds' molecular targets and binding modes. In particular, subsequent structure-based chemical optimization and target-based screening require a detailed understanding of the binding event. Here, we use directed evolution and whole-genome sequencing of a drug-sensitive S. cerevisiae strain to identify the yeast ortholog of TcCyp51, lanosterol-14-alpha-demethylase (TcCyp51), as the target of MMV001239, a benzamide compound with activity against Trypanosoma cruzi, the etiological agent of Chagas disease...
February 17, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/27934927/sensitisation-of-an-azole-resistant-aspergillus-fumigatus-strain-containing-the-cyp51a-related-mutation-by-deleting-the-srba-gene
#18
Daisuke Hagiwara, Akira Watanabe, Katsuhiko Kamei
Azoles are widely used for controlling fungal growth in both agricultural and medical settings. The target protein of azoles is CYP51, a lanosterol 14-α-demethylase involved in the biosynthesis of ergosterol. Recently, a novel azole resistance mechanism has arisen in pathogenic fungal species Aspergillus fumigatus. Resistant strains contain a 34-bp or 46-bp tandem repeat (TR) in the promoter of cyp51A, and have disseminated globally in a short period of time. In this study, we investigated whether an azole-resistant strain with a 46-bp TR (TR46/Y121F/T289A) could be sensitised to azoles by deletion of srbA, encoding a direct regulator of cyp51A...
December 9, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27907120/structural-and-functional-elucidation-of-yeast-lanosterol-14%C3%AE-demethylase-in-complex-with-agrochemical-antifungals
#19
Joel D A Tyndall, Manya Sabherwal, Alia A Sagatova, Mikhail V Keniya, Jacopo Negroni, Rajni K Wilson, Matthew A Woods, Klaus Tietjen, Brian C Monk
Azole antifungals, known as demethylase inhibitors (DMIs), target sterol 14α-demethylase (CYP51) in the ergosterol biosynthetic pathway of fungal pathogens of both plants and humans. DMIs remain the treatment of choice in crop protection against a wide range of fungal phytopathogens that have the potential to reduce crop yields and threaten food security. We used a yeast membrane protein expression system to overexpress recombinant hexahistidine-tagged S. cerevisiae lanosterol 14α-demethylase and the Y140F or Y140H mutants of this enzyme as surrogates in order characterize interactions with DMIs...
2016: PloS One
https://www.readbyqxmd.com/read/27905068/inhibition-of-mevalonate-pathway-and-synthesis-of-the-storage-lipids-in-human-liver-derived-and-non-liver-cell-lines-by-lippia-alba-essential-oils
#20
Sandra Montero-Villegas, Mónica Polo, Marianela Galle, Boris Rodenak-Kladniew, María Castro, Ana Ves-Losada, Rosana Crespo, Margarita García de Bravo
The essential oils (EOs) of Lippia alba, an herb extensively used as a folk medicine in Latin America, are today promoted as an effective means of eliminating problems caused by hyperlipemia. We hypothesized that L.alba EOs inhibited cholesterol and triacylglycerols synthesis and decreased the intracellular depots of those lipids (lipid droplets), mechanisms involving the induction of a hypolipidemic response. Our aim was, therefore, to evaluate the hypolipogenic capability of the EOs of four L. alba chemotypes on liver-derived (HepG2) and non-liver (A549) human cell lines and to identify the potential biochemical targets of those chemotypes, particularly within the mevalonate pathway (MP)...
November 30, 2016: Lipids
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