Article
Biochemistry & Molecular Biology
Bhaswati Banerjee, Olayemi Joseph Olajide, Giulia Bortolussi, Andres F. Muro
Summary: Bilirubin is a byproduct of heme metabolism, and Ugt1a1 is the enzyme responsible for its elimination. Dysfunctional Ugt1a1 can lead to the accumulation of unconjugated bilirubin in the brain, causing neuronal damage and death. Understanding alternative bilirubin detoxification mechanisms is crucial for developing new therapeutic strategies. Activation of alternative clearance pathways can partially improve hyperbilirubinemic conditions in the absence of Ugt1a1.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Pharmacology & Pharmacy
Zhe Shi, Xue Li, Yu-Man Zhang, Yi-Yao Zhou, Xiu-Feng Gan, Qiao-Ying Fan, Chen-Qing He, Tong Shi, Shu-Yun Zhang
Summary: This study investigates the molecular mechanisms of the inflammatory response in pyrene-caused mice liver injury and reveals the crucial role of the CAR gene in this process, leading to increased levels of SAAs and Th17 cells. Our findings suggest that serum SAAs may serve as a convenient biomarker for early diagnosis of liver inflammatory response caused by polycyclic aromatic hydrocarbons, including pyrene.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Article
Endocrinology & Metabolism
Ye Feng, Dan Xu, Xinran Cai, Meishu Xu, Wojciech G. Garbacz, Songrong Ren, Michael J. Jurczak, Chaohui Yu, Hui Wang, Wen Xie
Summary: The study found that GDM is a key risk factor for future development of metabolic disease, and CAR could be a therapeutic target for managing metabolic diseases sensitized by GDM.
Article
Biochemistry & Molecular Biology
Hangxing Huang, Change Cao, Zhimin Miao, Xiaoli Yang, Yong Lai
Summary: In this study, it was found that scutellarin can affect the expression of CYP3A4 and CYP2C19 in HepG2 and Caco-2 cells by regulating nuclear receptors PXR and CAR. Scutellarin inhibits the expression of CYP3A4 through PXR, and up-regulates CYP2C19 through CAR.
CURRENT MOLECULAR PHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Mireia Lopez-Riera, Rebeca Ortega, Luisa Hueso, Maria Carmen Montesinos, Mari Carmen Gomez-Cabrera, Maria Jesus Sanz, Jose T. Real, Laura Piqueras
Summary: This study demonstrates that CAR agonists can inhibit the early inflammatory response that precedes atherosclerosis by targeting various steps in the leukocyte recruitment cascade. This suggests that CAR agonists may serve as a new therapeutic approach to control inflammation associated with cardiovascular diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Pharmacology & Pharmacy
Lesley A. Stanley, C. Roland Wolf
Summary: The use of in vitro models for hepatic metabolism and toxicity assessment is essential for evaluating drug candidates. HepG2 and HepaRG cell lines are commonly used, but HepG2 cells have limitations and lack drug-metabolizing capacity. HepaRG cells are more hepatocyte-like but have variability in data possibly due to complex differentiation protocols. Standardized protocols and validation of P450 regulation mechanisms are needed to utilize HepaRG cells effectively.
DRUG METABOLISM REVIEWS
(2022)
Article
Food Science & Technology
Takumi Sato, Ryota Shizu, Yoshie Miura, Takuomi Hosaka, Yuichiro Kanno, Takamitsu Sasaki, Kouichi Yoshinari
Summary: This study identified possible direct and indirect activators of rCAR by measuring Cyp2b1 mRNA levels and performing reporter assays. It demonstrated the usefulness of these methods in evaluating rCAR activation by chemicals.
FOOD AND CHEMICAL TOXICOLOGY
(2022)
Review
Cell Biology
Leonida Rakateli, Rosanna Huchzermeier, Emiel P. C. van der Vorst
Summary: Xenobiotic receptors play a crucial role in both chemical sensing and detoxification as well as lipid metabolism regulation, particularly in relation to dyslipidemia.
Article
Biochemistry & Molecular Biology
Monicah N. Bwayi, Efren Garcia-Maldonado, Sergio C. Chai, Boer Xie, Shirish Chodankar, Andrew D. Huber, Jing Wu, Kavya Annu, William C. Wright, Hyeong-Min Lee, Jayaraman Seetharaman, Jingheng Wang, Cameron D. Buchman, Junmin Peng, Taosheng Chen
Summary: The interactions between nuclear receptors can fundamentally change our understanding of their biology. In this study, the molecular basis of crosstalk between the pregnane X receptor (PXR) and constitutive androstane receptor (CAR) is revealed, demonstrating the formation of a novel heterodimer and mutual inhibition. These findings not only change the perceived functional relationship between PXR and CAR, but also provide new perspectives for elucidating their role and designing approaches to regulate them.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Pharmacology & Pharmacy
Congrong Niu, Bill Smith, Yurong Lai
Summary: This study characterized the gene induction by ligands of CAR and AhR in human hepatocytes, showing distinct effects on metabolizing enzyme and drug transporter genes. Different inducers had varying degrees of effects on specific genes, highlighting the importance of assessing transporter gene inductions alongside metabolizing enzyme genes.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Nutrition & Dietetics
Dicson Sheeja Malar, Mani Iyer Prasanth, Kanika Verma, Anchalee Prasansuklab, Tewin Tencomnao
Summary: In this study, the mode of toxicity of Phenanthrene (Phe) in human keratinocytes was investigated, along with the protective effect of the ethanol extract of Hibiscus sabdariffa calyxes (HS). The results showed that Phe induced cytotoxicity through CAR/PXR/RXR-mediated activation of CYP1A1, leading to alterations in phase I and II metabolism genes. However, pre-treatment with HS extract inhibited CYP1A1 and attenuated the pathological changes caused by Phe exposure.
Article
Dermatology
Baochang Lai, Xinya Xie, Fan Li, Qi Cui, Erle Dang, Wenhuan Luo, Ning Wang, Yan Zheng, Gang Wang, Lei Xiao, Nanping Wang
Summary: The study demonstrates that CAR plays a pathogenic role in psoriasis and has the potential to be a target for its treatment. Xenobiotics and proinflammatory cytokines affect the expression of CAR and its target genes, further promoting the development of psoriatic skin lesions.
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2021)
Article
Environmental Sciences
Pham Thi Dau, Hiroshi Ishibashi, Le Huu Tuyen, Hiroki Sakai, Masashi Hirano, Eun-Young Kim, Hisato Iwata
Summary: This study evaluated the binding affinities of PCBs and PBDEs with the CAR_LBD of the Baikal seal and mouse using SPR biosensor, showing that PBDEs had higher binding affinities than PCBs for both CAR_LBDs; in silico docking simulations revealed that PBDEs had more non-covalent interactions with specific amino acid residues in both CAR_LBDs; the binding affinities were not consistent with the previously reported transactivation potencies of the congeners.
SCIENCE OF THE TOTAL ENVIRONMENT
(2022)
Article
Pharmacology & Pharmacy
Lena C. Preiss, Ruoqi Liu, Philip Hewitt, David Thompson, Katrin Georgi, Lassina Badolo, Volker M. Lauschke, Carl Petersson
Summary: This study utilized HepaRG cells and PXR, CAR KO cells to investigate the induction mechanisms of CYP3A4 and CYP2B6, revealing that most test compounds induced these enzymes primarily through PXR and to a lesser extent through CAR, while also implicating other non-NHR-driven induction mechanisms.
DRUG METABOLISM AND DISPOSITION
(2021)
Article
Biochemistry & Molecular Biology
Shin-Hun Juang, Min-Tsang Hsieh, Pei-Ling Hsu, Ju-Ling Chen, Hui-Kang Liu, Fong-Pin Liang, Sheng-Chu Kuo, Chen-Yuan Chiu, Shing-Hwa Liu, Chen-Hsi Chou, Tian-Shung Wu, Hsin-Yi Hung
Summary: In the study, 6,7-diprenoxycoumarin was identified as the most effective CAR activator, with modifications at the 6 position and unsaturated chains generally beneficial. The research also indicated that mimicking natural occurring coumarins for modification shed light on CAR studies.