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.
Article
Cell Biology
Fabiana Oliviero, Wendy Klement, Lucile Mary, Yannick Dauwe, Yannick Lippi, Claire Naylies, Veronique Gayrard, Nicola Marchi, Laila Mselli-Lakhal
Summary: Non-Alcoholic Fatty Liver Disease (NAFLD) is a common chronic liver disease, especially in obese individuals. This study suggests that the nuclear receptor CAR may play a role in the pathogenesis of NAFLD and could be a potential therapeutic target. In mice, deletion of CAR led to a NASH-like hepatic transcriptomic signature and astrogliosis in the hypothalamus of female mice.
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
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
Xuan Xiang, Houfu Wang, Wentao Zhou, Chenyu Wang, Peng Guan, Gang Xu, Qiang Zhao, Liuqin He, Yulong Yin, Tiejun Li
Summary: This study investigated the regulatory mechanism of different dietary levels of endogenous glutathione (GSH) supplementation on the intestinal barrier and antioxidant function in a paraquat-induced stress-weaned piglet model. The results showed that dietary 0.06% GSH supplementation improved the growth performance and reduced diarrhea rate of weaned piglets. GSH also protected against oxidative stress damage by regulating intestinal morphology, organelle, and permeability, as well as modulating antioxidant and anti-inflammatory gene expression.
Review
Biochemistry & Molecular Biology
Sarah Da Won Bae, Romario Nguyen, Liang Qiao, Jacob George
Summary: CAR is a receptor that is predominantly expressed in the liver and interacts with key signaling pathways related to drug, energy, and bilirubin metabolism. While studies in animal models suggest a potential role of CAR in tumorigenesis, recent research has shown species differences and a possible tumor-suppressive role of CAR in liver cancer in humans. This review highlights the need for further exploration of CAR's role in human diseases, particularly cancers, with a focus on its emerging functions in liver cancer.
BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER
(2021)
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
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
Biochemistry & Molecular Biology
Bhavna Sharma, Bhavya Sethi, Shashank Kumar, Raju Poddar, Amit Prasad, Shubha Rani Sharma
Summary: In this study, the interactions between scoparone and CAR were analyzed through computational simulation. It was found that scoparone can stably interact with CAR, thus activating CAR and preventing gallstone formation. These results provide valuable insights for further in vivo studies.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Pharmacology & Pharmacy
Maike Gaehrs, Dieter Schrenk
Summary: NDL-PCBs can suppress UV-induced apoptosis in rat hepatocytes by activating CAR and PXR, and the effects on apoptosis by CAR or PXR activators are specific to CAR or PXR.
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)
Review
Pharmacology & Pharmacy
Shuaiqian Men, Hongbing Wang
Summary: Phenobarbital (PB) is widely used as a research tool and has advanced our understanding of nuclear receptor-mediated drug metabolism, drug-drug interactions, energy homeostasis, and cell proliferation. PB activates CAR and PXR through an indirect signaling mechanism, involving dephosphorylation of Thr38 in CAR's DNA-binding domain. The species-specific role of PB in gene regulation determines its implications in various biological processes.
DRUG METABOLISM AND DISPOSITION
(2023)
Article
Toxicology
Amina Shehu, Junjie Zhu, Jianhua Li, Jie Lu, Deborah McMahon, Wen Xie, Frank J. Gonzalez, Xiaochao Ma
Summary: This study identified PXR and CAR as key modulators of COBI hepatotoxicity, which potentiate COBI hepatotoxicity through CYP3A4-dependent pathways. These findings can guide the safe use of COBI in the clinic by targeting PXR and CAR.
TOXICOLOGICAL SCIENCES
(2021)
Article
Pharmacology & Pharmacy
Yoshihiro Kobashigawa, Mana Namikawa, Mitsuhiro Sekiguchi, Yuki Inada, Soichiro Yamauchi, Yuu Kimoto, Kyo Okazaki, Yuya Toyota, Takashi Sato, Hiroshi Morioka
Summary: The constitutive active/androstane receptor (CAR) is a nuclear receptor involved in drug metabolism regulation. A novel system was developed for rapid evaluation of drug interactions with CAR, using differential scanning fluorometry (DSF) to confirm direct interactions. This method is easy to set up and beneficial for drug discovery purposes.
BIOLOGICAL & PHARMACEUTICAL BULLETIN
(2021)
Article
Oncology
John P. Thomson, Raffaele Ottaviano, Elif B. Unterberger, Harri Lempiainen, Arne Muller, Remi Terranova, Robert S. Illingworth, Shaun Webb, Alastair R. W. Kerr, Marcus J. Lyall, Amanda J. Drake, C. Roland Wolf, Jonathan G. Moggs, Michael Schwarz, Richard R. Meehan
Article
Toxicology
Karol L. Thompson, Eric Boitier, Tao Chen, Philippe Couttet, Heidrun Ellinger-Ziegelbauer, Manuela Goetschy, Gregory Guillemain, Masayuki Kanki, Janet Kelsall, Claire Mariet, Catherine de La Moureyre-Spire, Peter Mouritzen, Rounak Nassirpour, Raegan O'Lone, P. Scott Pine, Barry A. Rosenzweig, Tatiana Sharapova, Aaron Smith, Hidefumi Uchiyama, Jian Yan, Peter S. Yuen, Russ Wolfinger
TOXICOLOGICAL SCIENCES
(2016)
Article
Toxicology
Karin Brecht, Virginie Riebel, Philippe Couttet, Franziska Paech, Armin Wolf, Salah-Dine Chibout, Francois Pognan, Stephan Kraehenbuehl, Marianne Uteng
TOXICOLOGY IN VITRO
(2017)
Article
Biotechnology & Applied Microbiology
Russell D. Wolfinger, Sudheer Beedanagari, Eric Boitier, Tao Chen, Philippe Couttet, Heidrun Ellinger-Ziegelbauer, Gregory Guillemain, Claire Mariet, Peter Mouritzen, Raegan O'Lone, P. Scott Pine, Tatiana Sharapova, Jian Yan, Peter S. Yuen, Karol L. Thompson
Article
Chemistry, Medicinal
Juraj Velcicky, Ursula Bodendorf, Pascal Rigollier, Robert Epple, Daniel R. Beisner, Danilo Guerini, Philip Smith, Bo Liu, Roland Feifel, Peter Wipfli, Reiner Aichholz, Philippe Couttet, Ina Dix, Toni Widmer, Ben Wen, Trixi Brandl
JOURNAL OF MEDICINAL CHEMISTRY
(2018)
Article
Toxicology
Heiko S. Schadt, Armin Wolf, Joerg Andreas Mahl, Kuno Wuersch, Philippe Couttet, Marianne Schwald, Audrey Fischer, Mathilde Lienard, Corinne Emotte, Chi-Hse Teng, Elizabeth Skuba, Terrilyn A. Richardson, Luigi Manenti, Andreas Weiss, Diana Graus Porta, Robin A. Fairhurst, Gerd A. Kullak-Ublick, Salah-Dine Chibout, Francois Pognan, William Kluwe, Jacqueline Kinyamu-Akunda
TOXICOLOGICAL SCIENCES
(2018)
Article
Pharmacology & Pharmacy
Francois Pognan, Philippe Couttet, Ivan Demin, Birgit Jaitner, Yinuo Pang, Ronenn Roubenoff, Esther Sutter, Yoav Timsit, Marie Anne Valentin, Beate Vogel, Gaetane Woerly, Armin Wolf, Ursula Schramm
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
(2019)
Article
Immunology
Diethilde Theil, Paul Smith, Catherine Huck, Yoann Gilbart, Algirdas Kakarieka, David Leppert, Celine Rauld, Cindy Schmid, Reto Baumgartner, Nathalie Stuber, Francisco Cordoba, Valerie Dubost, Katy Darribat, Magali Jivkov, Wilfried Frieauff, Rainer Kneuer, Markus Stoeckli, Stefan Reinker, Keith Mansfield, Jose M. Carballido, Philippe Couttet, Gisbert Weckbecker
FRONTIERS IN IMMUNOLOGY
(2019)
Article
Oncology
Andreas Weiss, Flavia Adler, Alexandra Buhles, Christelle Stamm, Robin A. Fairhurst, Michael Kiffe, Dario Sterker, Mario Centeleghe, Markus Wartmann, Jacqueline Kinyamu-Akunda, Heiko S. Schadt, Philippe Couttet, Armin Wolf, Youzhen Wang, Patrizia Barzaghi-Rinaudo, Masato Murakami, Audrey Kauffmann, Thomas Knoepfel, Nicole Buschmann, Catherine Leblanc, Robert Mah, Pascal Furet, Jutta Blank, Francesco Hofmann, William R. Sellers, Diana Graus Porta
MOLECULAR CANCER THERAPEUTICS
(2019)
Article
Chemistry, Medicinal
Robin A. Fairhurst, Thomas Knoepfel, Nicole Buschmann, Catherine Leblanc, Robert Mah, Milen Todorov, Pierre Nimsgern, Sebastien Ripoche, Michel Niklaus, Nicolas Warin, Van Huy Luu, Mario Madoerin, Jasmin Wirth, Diana Graus-Porta, Andreas Weiss, Michael Kiffe, Markus Wartmann, Jacqueline Kinyamu-Akunda, Dario Sterker, Christelle Stamm, Flavia Adler, Alexandra Buhles, Heiko Schadt, Philippe Couttet, Jutta Blank, Inga Galuba, Jorg Trappe, Johannes Voshol, Nils Ostermann, Chao Zou, Jorg Berghausen, Alberto Del Rio Espinola, Wolfgang Jahnke, Pascal Furet
JOURNAL OF MEDICINAL CHEMISTRY
(2020)
Article
Cell & Tissue Engineering
Myriam Lemmens, Juliane Perner, Leon Potgeter, Michael Zogg, Sineha Thiruchelvam, Matthias Mueller, Thierry Doll, Annick Werner, Yoann Gilbart, Philippe Couttet, Hans-Jorg Martus, Silvana Libertini
Summary: This study presents an approach to identify potential marker genes for residual undifferentiated iPSCs in iPSC-derived cells. By screening and validating specific genes, a set of highly specific and sensitive markers for quality assessment of iPSC-derived products was identified.
Article
Cell Biology
Lukas-Adrian Gurzeler, Marion Link, Yvonne Ibig, Isabel Schmidt, Olaf Galuba, Julian Schoenbett, Christelle Gasser-Didierlaurant, Christian N. Parker, Xiaohong Mao, Francis Bitsch, Markus Schirle, Philipp Couttet, Frederic Sigoillot, Jana Ziegelmueller, Anne-Christine Uldry, Wojciech Teodorowicz, Niko Schmiedeberg, Oliver Muhlemann, Jurgen Reinhardt
Summary: This study discovered two potent readthrough promoters that can restore full-length functional proteins in disease models. Unlike other readthrough promoters, these compounds stimulate premature termination codon suppression by promoting the degradation of the translation termination factor eRF1.
Article
Toxicology
Francois Pognan, Chiara Buono, Philippe Couttet, Jean-Rene Galarneau, Yoav Timsit, Armin Wolf
Summary: Sotuletinib caused liver enzyme elevation without hepatocellular lesions, possibly due to the inhibition of Kupffer cells via the CSF1 pathway. However, the release of biomarkers from other organs or unseen liver lesions cannot be excluded.
CURRENT RESEARCH IN TOXICOLOGY
(2022)
Review
Toxicology
Brian N. Chorley, Elnaz Atabakhsh, Graeme Doran, Jean-Charles Gautier, Heidrun Ellinger-Ziegelbauer, David Jackson, Tatiana Sharapova, Peter S. T. Yuen, Rachel J. Church, Philippe Couttet, Roland Froetschl, James McDuffie, Victor Martinez, Parimal Pande, Lauren Peel, Conor Rafferty, Frank J. Simutis, Alison H. Harrill
Summary: miRNAs, small non-coding RNA molecules, regulate RNA expression and can serve as indicators of cellular processes. Despite enthusiasm for using miRNAs as biomarkers, lack of standard methods and biological interpretation uncertainty have hindered their routine noninvasive use.
CRITICAL REVIEWS IN TOXICOLOGY
(2021)
Article
Toxicology
Celine Parmentier, Philippe Couttet, Armin Wolf, Thomas Zaccharias, Bruno Heyd, Philippe Bachellier, Marianne Uteng, Lysiane Richert
ARCHIVES OF TOXICOLOGY
(2017)