A Systematic Gene Expression Screen of Caenorhabditis elegans Cytochrome P450 Genes Reveals CYP35 as Strongly Xenobiotic Inducible

2001 ◽  
Vol 395 (2) ◽  
pp. 158-168 ◽  
Author(s):  
Ralph Menzel ◽  
Thierry Bogaert ◽  
Rudolf Achazi
2021 ◽  
Vol 62 (4) ◽  
pp. 316-324
Author(s):  
Susan Omar Rasool ◽  
Ata Mirzaei Nahr ◽  
Sania Eskandari ◽  
Milad Hosseinzadeh ◽  
Soheila Asoudeh Moghanloo ◽  
...  

While COVID-19 liver injuries have been reported in various studies, concerns are raised about disease-drug reactions in COVID-19 patients. In this study, we examined the hypothesis of gene-disease interactions in an in-silico model of gene expression to seek changes in cytochrome P450 genes. The Gene Expression Omnibus dataset of the liver autopsy in deceased COVID-19 patients (GSE150316) was used in this study. Non-alcoholic fatty liver biopsies were used as the control (GSE167523). Besides, gene expression analysis was performed using the DESeq/EdgeR method. The GO databases were used, and the paths were set at p<0.05. The drug-gene interaction database (DGIdb) was searched for interactions. According to the results, 5,147 genes were downregulated, and 5,122 genes were upregulated in SARS-CoV-2 compared to healthy livers. Compared to the cytochromes, 34 cytochromes were downregulated, while 4 cytochromes were upregulated among the detected differentially expressed genes (DEG). The drug-gene interaction database (DGIdb) provided a list of medications with potential interactions with COVID-19 as well as metacetamol, phenethyl isocyanate, amodiaquine, spironolactone, amiloride, acenocoumarol, clopidogrel, phenprocoumon, trimipramine, phenazepam, etc. Besides, dietary compounds of isoflavones, valerian, and coumarin, as well as caffeine metabolism were shown to have possible interactions with COVID-19 disease. Our study showed that expression levels of cytochrome P450 genes could get altered following COVID-19. In addition, a drug-disease interaction list is recommended to be used for evaluations in clinical considerations in further studies.


2002 ◽  
Vol 2002 (Fall) ◽  
Author(s):  
Ralph Menzel ◽  
Kerstin Reichert ◽  
Matthias R??del

2011 ◽  
Vol 435 (3) ◽  
pp. 689-700 ◽  
Author(s):  
Mandy Kosel ◽  
Waltraud Wild ◽  
Alexandra Bell ◽  
Michael Rothe ◽  
Carsten Lindschau ◽  
...  

Caenorhabditis elegans harbours several CYP (cytochrome P450) genes that are homologous with mammalian CYP isoforms important to the production of physiologically active AA (arachidonic acid) metabolites. We tested the hypothesis that mammals and C. elegans may share similar basic mechanisms of CYP-dependent eicosanoid formation and action. We focused on CYP33E2, an isoform related to the human AA-epoxygenases CYP2C8 and CYP2J2. Co-expression of CYP33E2 with the human NADPH–CYP reductase in insect cells resulted in the reconstitution of an active microsomal mono-oxygenase system that metabolized EPA (eicosapentaenoic acid) and, with lower activity, also AA to specific sets of regioisomeric epoxy- and hydroxy-derivatives. The main products included 17,18-epoxyeicosatetraenoic acid from EPA and 19-hydroxyeicosatetraenoic acid from AA. Using nematode worms carrying a pCYP33E2::GFP reporter construct, we found that CYP33E2 is exclusively expressed in the pharynx, where it is predominantly localized in the marginal cells. RNAi (RNA interference)-mediated CYP33E2 expression silencing as well as treatments with inhibitors of mammalian AA-metabolizing CYP enzymes, significantly reduced the pharyngeal pumping frequency of adult C. elegans. These results demonstrate that EPA and AA are efficient CYP33E2 substrates and suggest that CYP–eicosanoids, influencing in mammals the contractility of cardiomyocytes and vascular smooth muscle cells, may function in C. elegans as regulators of the pharyngeal pumping activity.


2019 ◽  
Vol 220 (3) ◽  
pp. 467-475 ◽  
Author(s):  
Jacob M Riveron ◽  
Silvie Huijben ◽  
Williams Tchapga ◽  
Magellan Tchouakui ◽  
Murielle J Wondji ◽  
...  

Abstract Background Insecticide resistance poses a serious threat to insecticide-based interventions in Africa. There is a fear that resistance escalation could jeopardize malaria control efforts. Monitoring of cases of aggravation of resistance intensity and its impact on the efficacy of control tools is crucial to predict consequences of resistance. Methods The resistance levels of an Anopheles funestus population from Palmeira, southern Mozambique, were characterized and their impact on the efficacy of various insecticide-treated nets established. Results A dramatic loss of efficacy of all long-lasting insecticidal nets (LLINs), including piperonyl butoxide (PBO)–based nets (Olyset Plus), was observed. This An. funestus population consistently (2016, 2017, and 2018) exhibited a high degree of pyrethroid resistance. Molecular analyses revealed that this resistance escalation was associated with a massive overexpression of the duplicated cytochrome P450 genes CYP6P9a and CYP6P9b, and also the fixation of the resistance CYP6P9a_R allele in this population in 2016 (100%) in contrast to 2002 (5%). However, the low recovery of susceptibility after PBO synergist assay suggests that other resistance mechanisms could be involved. Conclusions The loss of efficacy of pyrethroid-based LLINs with and without PBO is a concern for the effectiveness of insecticide-based interventions, and action should be taken to prevent the spread of such super-resistance.


2017 ◽  
Vol 72 (10) ◽  
pp. 1305-1310 ◽  
Author(s):  
Alexander Mendenhall ◽  
Matthew M Crane ◽  
Patricia M Tedesco ◽  
Thomas E Johnson ◽  
Roger Brent

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