Search results for: P450
#36473170 2022/12/06 To Up
Probing the Role of CYP2 Enzymes in the Atropselective Metabolism of Polychlorinated Biphenyls Using Liver Microsomes from Transgenic Mouse Models.Chiral polychlorinated biphenyls (PCB) are environmentally relevant developmental neurotoxicants. Because their hydroxylated metabolites (OH-PCBs) are also neurotoxic, it is necessary to determine how PCB metabolism affects the developing brain, for example, in mouse models. Because the cytochrome P450 isoforms involved in the metabolism of chiral PCBs remain unexplored, we investigated the metabolism of PCB 91 (2,2',3,4',6-pentachlorobiphenyl), PCB 95 (2,2',3,5',6-pentachlorobiphenyl), PCB 132 (2,2',3,3',4,6'-hexachlorobiphenyl), and PCB 136 (2,2',3,3',6,6'-hexachlorobiphenyl) using liver microsomes from male and female -null, -null, and wild-type mice. Microsomes, pooled by sex, were incubated with 50 μM PCB for 30 min, and the levels and enantiomeric fractions of the OH-PCBs were determined gas chromatographically. All four PCB congeners appear to be atropselectively metabolized by CYP2A(4/5)BGS and CYP2F2 enzymes in a congener- and sex-dependent manner. The OH-PCB metabolite profiles of PCB 91 and PCB 132, PCB congeners with one -chlorine substituent, differed between null and wild-type mice. No differences in the metabolite profiles were observed for PCB 95 and PCB 136, PCB congeners without a -chlorine group. These findings suggest that -null and -null mice can be used to study how a loss of a specific metabolic function (e.g., deletion of or ) affects the toxicity of chiral PCB congeners.
Hans-Joachim Lehmler, Eric Uwimana, Laura E Dean, Nataliia Kovalchuk, Qing-Yu Zhang, Xinxin Ding
1469 related Products with: Probing the Role of CYP2 Enzymes in the Atropselective Metabolism of Polychlorinated Biphenyls Using Liver Microsomes from Transgenic Mouse Models.100 1100 μg
#36472117 // To Up
Heavy Metals, Halogenated Hydrocarbons, Phthalates, Glyphosate, Cordycepin, Alcohol, Drugs, and Herbs, Assessed for Liver Injury and Mechanistic Steps.Aluminum, arsenic, cadmium, chromium, cobalt, copper, iron, lead, mercury, nickel, thallium, titanium, zinc, carbon tetrachloride, phthalates, glyphosate, alcohol, drugs, and herbs are under discussion having the potential to injure the human liver, but allocation of the injury to the hepatotoxicant as exact cause is difficult for physicians and requires basic clinical knowledge of toxicology details. Liver injury occurs at a variable extent depending on the dose, mostly reproducible in animal models that allow studies on molecular steps leading to the hepatocellular injury. These exogenous hepatotoxins may cause an overproduction of reactive oxidative species (ROS), which are generated during microsomal or mitochondrial oxidative stress from incomplete oxygen split and trigger the injury if protective antioxidant capacities are reduced. Primary subcelluar target organelles involved are liver mitochondria through lipid peroxidation of membrane structures and the action of free radicals such as singlet radical 1O2, superoxide radical HO•2, hydrogen peroxide H2O2, hydroxyl radical HO•, alkoxyl radical RO•, and peroxyl radical ROO•. They attempt covalent binding to macromolecular structural proteins. As opposed to inorganic chemicals, liver injury due to chemicals with an organic structure proceedes via the hepatic microsomal cytochrome P450 with its different isoforms. In sum, many exogenous chemicals may have the potential of liver injury triggerd by overproduced ROS leading primarily to impairment of mitochondial functions in the course of structural mitochondial membrane dearrangement. As clinical data were often incomplete, future clinical prototols should focus on meeting liver injury criteria, exclusion of alternative causes, a robust causality evaluation management, and obtaining liver histology if clinically indicated and of benefit for the patient.
Rolf Teschke, Tran Dang Xuan
2794 related Products with: Heavy Metals, Halogenated Hydrocarbons, Phthalates, Glyphosate, Cordycepin, Alcohol, Drugs, and Herbs, Assessed for Liver Injury and Mechanistic Steps.100 mg200ug200ul200 10 mg 25 MG25 mg100 mg10 mg100ug200ug
#36472108 // To Up
PGRMC? Grand-Scale Biology from Early Eukaryotes and Eumetazoan Animal Origins.The title usage of 'from where have you come' is from a now dead language (Latin) that foundationally influenced modern English (not the major influence, but an essential formative one). This is an apt analogy for how both the ancient eukaryotic and eumetazoan functions of PGRMC proteins (PGRMC1 and PGRMC2 in mammals) probably influence modern human biology: via a formative trajectory from an evolutionarily foundational fulcrum. There is an arguable probability, although not a certainty, that PGRMC-like proteins were involved in eukaryogenesis. If so, then the proto-eukaryotic ancestral protein is modelled as having initiated the oxygen-induced and CYP450 (Cytochrome P450)-mediated synthesis of sterols in the endoplasmic reticulum to regulate proto-mitochondrial activity and heme homeostasis, as well as having enabled sterol transport between endoplasmic reticulum (ER) and mitochondria membranes involving the actin cytoskeleton, transport of heme from mitochondria, and possibly the regulation/origins of mitosis/meiosis. Later, during animal evolution, the last eumetazoan common ancestor (LEUMCA) acquired PGRMC phosphorylated tyrosines coincidentally with the gastrulation organizer, Netrin/deleted in colorectal carcinoma (DCC) signaling, muscle fibers, synapsed neurons, and neural recovery via a sleep-like process. Modern PGRMC proteins regulate multiple functions, including CYP450-mediated steroidogenesis, membrane trafficking, heme homeostasis, glycolysis/Warburg effect, fatty acid metabolism, mitochondrial regulation, and genomic CpG epigenetic regulation of gene expression. The latter imposes the system of differentiation status-sensitive cell-type specific proteomic complements in multi-tissued descendants of the LEUMCA. This paper attempts to trace PGRMC functions through time, proposing that key functions were involved in early eukaryotes, and were later added upon in the LEUMCA. An accompanying paper considers the implications of this awareness for human health and disease.
Michael A Cahill
2295 related Products with: PGRMC? Grand-Scale Biology from Early Eukaryotes and Eumetazoan Animal Origins.100ug1mg0.1mg1 kit500 mg1mg1mg50 ug 25 mg2.5 lt10mg1mg
#36472037 // To Up
[Schisandrin C improves acetaminophen-induced liver injury in mice by regulating Nrf2 signaling pathway].Excess acetaminophen(APAP) can be converted by the cytochrome P450 system to the toxic metabolite N-acetyl-p-benzoquinoneimine(NAPQI), which consumes glutathione(GSH). When GSH is depleted, NAPQI covalently binds with proteins, inducing mitochondrial dysfunction and oxidative stress and thereby leading to hepatotoxicity. Schisandrin C(SinC) is a dibenzocyclooctadiene derivative isolated from Schisandra chinensis. Although there is some evidence showing that SinC has hepatoprotective activity, its protective effect and mechanism on APAP-induced liver injury remain unclear. In this paper, an acute liver injury mouse model was established by intraperitoneal injection of APAP at a dose of 400 mg·kg~(-1) to evaluate the effect of SinC administration on the APAP-induced liver injury and its mechanism through an animal experiment. At the same time, a potential candidate drug was provi-ded for traditional Chinese medicine(TCM) prevention and treatment of overdose APAP-induced liver injury. In the APAP-induced liver injury mouse model, we found that SinC can relieve hepatic histopathological lesions and significantly reduce the activities of alanine aminotransferase(ALT), aspartate aminotransferase(AST) and alkaline phosphatase(ALP). It was also capable of increasing the content of GSH and superoxide dismutase(SOD) and decreasing the levels of total bilirubin(TBIL), direct bilirubin(DBIL), malondialdehyde(MDA), interleukin-6(IL-6) and tumor necrosis factor-α(TNF-α). Further analysis showed that SinC decreased the content of CYP2 E1 in liver tissues at protein and mRNA levels and increased nuclear factor erythroid 2-related factor 2(Nrf2) and the expression of its downstream targets(including HO-1, NQO1 and GCLC). Taken together, the above results indicate that SinC can alleviate APAP-induced liver injury by reducing the expression of CYP2 E1, suppressing apoptosis, improving inflammatory response and activating the Nrf2 signaling pathway to inhibit oxidative stress.
Wen-Zhang Dai, Zhao-Fang Bai, Ting-Ting He, Xiao-Yan Zhan, Qiang Li, Jing Zhao, Xiao-He Xiao
1522 related Products with: [Schisandrin C improves acetaminophen-induced liver injury in mice by regulating Nrf2 signaling pathway].2 Pieces/Box2 Pieces/Box2 Pieces/Box2 Pieces/Box2 Pieces/Box2 Pieces/Box2 Pieces/Box2 Pieces/Box2 Pieces/Box2 Pieces/Box
#36472013 // To Up
[Effects of Gukang Capsules on activity and protein expression of hepatic cytochrome P450 enzymes in rats].Gukang Capsules are often used in combination with drugs to treat fractures, osteoarthritis, and osteoporosis. Cytochrome P450(CYP450) mainly exists in the liver and participates in the oxidative metabolism of a variety of endogenous and exogenous substances and serves as an important cause of drug-metabolic interactions and adverse reactions. Therefore, it is of great significance to study the effect of Gukang Capsules on the activity and expression of CYP450 for increasing its clinical rational medication and improving the safety of drug combination. In this study, the Cocktail probe method was used to detect the changes in the activities of CYP1A2, CYP3A2, CYP2C11, CYP2C19, CYP2D4, and CYP2E1 in rat liver after treatment with high-, medium-and low-dose Gukang Capsules. The rat liver microsomes were extracted by the calcium chloride method, and protein expression of the above six CYP isoform enzymes was detected by Western blot. The results showed that the low-dose Gukang Capsules could induce CYP3A2 and CYP2D4 in rats, medium-dose Gukang Capsules had no effect on them, and high-dose Gukang Capsules could inhibit them in rats. The high-dose Gukang Capsules did not affect CYP2C11 in rats, but low-and medium-dose Gukang Capsules could induce CYP2C11 in rats. Gukang Capsules could inhibit CYP2C19 in rats and induce CYP1A2 in a dose-independent manner, but did not affect CYP2E1. If Gukang Capsules were co-administered with CYP1A2, CYP2C19, CYP3A2, CYP2C11, and CYP2D4 substrates, the dose should be adjusted to avoid drug interactions.
Chang Yang, Jing Li, Jia Sun, Ding-Yan Lu, Shuai-Shuai Chen, Yong-Jun Li, Yong-Lin Wang, Ting Liu
1001 related Products with: [Effects of Gukang Capsules on activity and protein expression of hepatic cytochrome P450 enzymes in rats].1mg1 Set1 Set1 Set100 μg1 Set5ug100ug Lyophilized1 Set1 Set
#36469695 2022/12/05 To Up
Antiplasmodial Asperterpenoids from Two Transformants with Heterologous Expression of Sesterterpene Genes.The synthetic biology approach enables efficient and directional mining of target compounds during drug discovery. Ten new asperterpenoids (-) and five known analogues (-), possessing a rare 5/7/3/6/5 skeleton, were obtained from two transformants with heterologous expression of a terpene cyclase gene with one or two P450 genes / under the guidance of molecular networking. Their planar structures were determined by 1D and 2D NMR and HR-ESI-MS. The absolute configurations of compounds and - were determined by single crystal X-ray diffraction, and those of compounds - and - were compared with the ECD of known compounds. Seven of all the compounds are the first asperterpenoid oxidation products at C-17 or at C-25. In bioassay, compounds -, - and - displayed moderate to strong eliminating activities against chloroquine-sensitive strain (37) with EC values ranging from 2.1 to 19.3 μM. The structure-activity relationship (SAR) was discussed, which showed that substituents at C-3, C-11, C-17, C-18, and C-23 of asperterpenoids significantly affected anti-plasma parasite activity.
Wencong Yang, Tao Chen, Yan Chen, Qi Tan, Yanghui Ou, Gang Li, Bo Wang, Dan Hu, Hongliang Yao, Zhigang She
1547 related Products with: Antiplasmodial Asperterpenoids from Two Transformants with Heterologous Expression of Sesterterpene Genes.1 kit(s) 100ug 25UG1 set
#36468547 2022/12/05 To Up
Systematic Optimization of HPO-CPR to Boost (+)-Nootkatone Synthesis in Engineered .As an important and expensive natural sesquiterpene compound in grapefruit, the interest in (+)-nootkatone is stimulated by its strong grapefruit-like odor and physiological activities, which induce efforts for its microbial production. However, the low catalytic efficiency of the cytochrome P450-P450 reductase (HPO-CPR) system is the main challenge. We developed a high-throughput screening (HTS) method using the principle of the color reaction between carbonyl compounds and 2,4-dinitrophenylhydrazine (DNPH), which could rapidly screen the activity of candidate HPO mutants. After optimizing the pairing of HPO and CPR and through semirational design, the optimal mutant HPO_M18 with catalytic performance 2.54 times that of the initial was obtained. An encouraging (+)-nootkatone titer of 2.39 g/L was achieved through two-stage fed-batch fermentation after metabolic engineering and endoplasmic reticulum engineering, representing the highest titer reported to date. Our findings lay the foundation for the development of an economically viable bioprocess for (+)-nootkatone.
Tong Liu, Wen Li, Hefeng Chen, Tao Wu, Chaoyi Zhu, Min Zhuo, Shuang Li
2645 related Products with: Systematic Optimization of HPO-CPR to Boost (+)-Nootkatone Synthesis in Engineered .1mg1 kit 1 G500 gm.100 μg1 kit100 mg96 wells50100
#36468470 2022/07/25 To Up
Sequential anti-inflammatory and osteogenic effects of a dual drug delivery scaffold loaded with parthenolide and naringin in periodontitis.Our pilot study showed that a 3-dimensional dual drug delivery scaffold (DDDS) loaded with Chinese herbs significantly increased the regenerated bone volume fraction. This study aimed to confirm the synergistic anti-inflammatory and osteogenic preclinical effects of this system.
Rui Chen, Mengting Wang, Qiaoling Qi, Yanli Tang, Zhenzhao Guo, Shuai Wu, Qiyan Li
2148 related Products with: Sequential anti-inflammatory and osteogenic effects of a dual drug delivery scaffold loaded with parthenolide and naringin in periodontitis.0.1 mg1000 1 ml100ul100 μg100ul1000 TESTS/0.65ml100.00 ul200 100 μg100ug100 μg
#36466761 2022/10/31 To Up
Bisphenol A is a carcinogen that induces lipid accumulation, peroxisome proliferator‑activated receptor‑γ expression and liver disease.Bisphenol (BP) A is an exogenous endocrine disruptor that mimics hormones closely associated with health complications, e.g., obesity and cancers. The present study aimed to evaluate the effects of BPA on human liver cells and tissue. The peroxisome proliferator-activated receptor (PPAR)-γ expression profile across tumour samples and paired normal tissue was first analysed using GEPIA. Subsequently, BPA-treated liver THLE-2 cell viability was evaluated using an MTT assay. Clusterin, PPARα and PPARγ gene expression in BPA-treated THLE-2 cells was assessed using GEPIA before validating the gene expression using real-time PCR and analysing overall survival using TCGA data in GEPIA. Cytoplasmic lipid accumulation was examined in BPA-treated THLE-2 cells using Oil Red O staining, and liver tissue was examined using haematoxylin and eosin staining. Finally, cytochrome P450 (CYP) gene expression was assessed in BPA-treated THLE-2 cells using real-time PCR. PPARγ is likely the primary nuclear receptor protein involved in lipid accumulation in THLE-2 cells following BPA treatment and is associated with liver disease. THLE-2 cells exposed to BPA showed a decrease in viability and lipid accumulation after 48 h treatment. Higher PPARγ gene expression was significantly associated with survival of patients with liver cancer, with an average survival time of <80 months. Haematoxylin and eosin-stained sections showed notable disruption of the liver architecture in tissue exposed to BPA. Downregulated CYP1A1 and CYP1B1 gene expression implied that BPA-treated THLE-2 cells decreased capacity for carcinogen metabolism, while upregulated CYP2S1 gene expression exerted minimal cytotoxicity. The present study revealed that BPA served as a carcinogen, enhanced tumorigenesis susceptibility and may induce other types of liver disease.
Layla Qasim Ismael, Ahmed Rashid Abdulhameed, Yong Yoke Keong, Muhammad Nazrul Hakim Abdullah, Hasnah Bahari, Tan Jun Jie, Khoo Boon Yin
1905 related Products with: Bisphenol A is a carcinogen that induces lipid accumulation, peroxisome proliferator‑activated receptor‑γ expression and liver disease.100ug Lyophilized0.1ml100ug Lyophilized100ug Lyophilized100ug Lyophilized100ug Lyophilized100ug Lyophilized100ug Lyophilized100ug Lyophilized100 100ug Lyophilized100ug Lyophilized
#36466247 2022/11/16 To Up
A meta-quantitative trait loci analysis identified consensus genomic regions and candidate genes associated with grain yield in rice.Improving grain yield potential in rice is an important step toward addressing global food security challenges. The metaQTL analysis offers stable and robust QTLs irrespective of the genetic background of mapping populations and phenotype environment and effectively narrows confidence intervals (CI) for candidate gene (CG) mining and marker-assisted selection improvement. To achieve these aims, a comprehensive bibliographic search for grain yield traits (spikelet fertility, number of grains per panicle, panicles number per plant, and 1000-grain weight) QTLs was conducted, and 462 QTLs were retrieved from 47 independent QTL research published between 2002 and 2022. QTL projection was performed using a reference map with a cumulative length of 2,945.67 cM, and MQTL analysis was conducted on 313 QTLs. Consequently, a total of 62 MQTLs were identified with reduced mean CI (up to 3.40 fold) compared to the mean CI of original QTLs. However, 10 of these MQTLs harbored at least six of the initial QTLs from diverse genetic backgrounds and environments and were considered the most stable and robust MQTLs. Also, MQTLs were compared with GWAS studies and resulted in the identification of 16 common significant loci modulating the evaluated traits. Gene annotation, gene ontology (GO) enrichment, and RNA-seq analyses of chromosome regions of the stable MQTLs detected 52 potential CGs including those that have been cloned in previous studies. These genes encode proteins known to be involved in regulating grain yield including cytochrome P450, zinc fingers, MADs-box, AP2/ERF domain, F-box, ubiquitin ligase domain protein, homeobox domain, DEAD-box ATP domain, and U-box domain. This study provides the framework for molecular dissection of grain yield in rice. Moreover, the MQTLs and CGs identified could be useful for fine mapping, gene cloning, and marker-assisted selection to improve rice productivity.
Kelvin Dodzi Aloryi, Nnaemeka Emmanuel Okpala, Aduragbemi Amo, Semiu Folaniyi Bello, Selorm Akaba, Xiaohai Tian
1356 related Products with: A meta-quantitative trait loci analysis identified consensus genomic regions and candidate genes associated with grain yield in rice.16 Arrays/Slide100 ml.300 units25 ml.16 Arrays/Slide16 Arrays/Slide16 Arrays/Slide1 mg16 Arrays/Slide1 Set1 Set
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