Article
Chemistry, Medicinal
Frauke Antoni, David Wifling, Guenther Bernhardt
Summary: This study focused on improving the solubility of ABCG2 inhibitors through a fragment-based approach, resulting in the discovery of novel inhibitors with improved solubility. These inhibitors exhibited good resistance in experiments, were non-toxic, and remained stable under various conditions.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Orsolya Mozner, Boglarka Zambo, Zsuzsa Bartos, Anna Gergely, Kata Sara Szabo, Balint Jezso, Agnes Telbisz, Gyoergy Varady, Laszlo Homolya, Tamas Hegedus, Balazs Sarkadi
Summary: This study analyzed the effects of variants in the unresolved cytoplasmic region of the ABCG2 multidrug transporter on protein function and trafficking. It was found that the K360del variant increased membrane expression and cellular trafficking of ABCG2, while alanine replacements of neighboring lysines had no significant effect on transport function.
Article
Agriculture, Dairy & Animal Science
Ziyong Xu, Mei Li, Wang Lu, Liping Wang, Yujuan Zhang
Summary: This study investigates the role of chicken xenobiotic receptor (CXR) in the regulation of breast cancer resistance protein (BCRP). The results show that CXR is involved in the regulation of BCRP gene expression and protein activity in chickens. Activation of CXR by metyrapone upregulates BCRP expression and transporter activity. Co-administration of metyrapone affects the pharmacokinetic behavior of orally administered BCRP substrate.
Article
Biochemistry & Molecular Biology
Julia Kowal, Dongchun Ni, Scott M. Jackson, Ioannis Manolaridis, Henning Stahlberg, Kaspar P. Locher
Summary: In this study, three cryo-EM structures of human ABCG2 bound to anticancer drugs tariquidar, topotecan, and mitoxantrone were presented, revealing the binding pocket details and functional importance of key residues. Mutagenesis experiments and 3D variability analysis provided further insights into the mechanisms by which ABCG2 distinguishes between inhibitors and substrates.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Agnes Angyal, Zsofia Penzes, Shahrzad Alimohammadi, Dorottya Horvath, Lili Takacs, Gyorgy Vereb, Barbara Zsebik, Tamas Biro, Kinga Fanni Toth, Erika Lisztes, Balazs Istvan Toth, Attila Olah, Attila Gabor Szollosi
Summary: The study found that human corneal epithelial cells express members of the endocannabinoid system, playing a role in inflammatory responses. Despite previous reports on the anti-inflammatory potential of endocannabinoids, their effects on the immune phenotype of human corneal epithelium may be more complex and context dependent.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Robert Eckenstaler, Ralf A. Benndorf
Summary: Urate homeostasis in humans is a complex and highly heritable process that involves metabolic urate biosynthesis, renal urate reabsorption, and renal and extrarenal urate excretion. ABCG2 plays a crucial role in urate transport and is associated with early-onset gout.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Environmental Sciences
Emily S. Barrett, Zorimar Rivera-Nunez, Kylie Getz, Pamela Ohman-Strickland, Ranran Zhang, Danielle Kozlosky, Cathleen L. Doherty, Brian T. Buckley, Jessica Brunner, Richard K. Miller, Thomas G. O'Connor, Lauren M. Aleksunes
Summary: This study assessed the protective role of the BCRP gene in prenatal cadmium exposure. It was found that individuals with a reduced function polymorphism in the BCRP gene were more vulnerable to higher cadmium exposure in the placenta, which adversely affected fetal growth. This suggests that reduced function of the BCRP gene may increase the risk of smaller placental and fetal size associated with maternal cadmium exposure.
ENVIRONMENTAL RESEARCH
(2023)
Article
Pharmacology & Pharmacy
Melissa L. Kozakiewicz, Jie Zhang, Sandra Leone-Kabler, Liliya M. Yamaleyeva, Anna G. McDonald, Brian C. Brost, Allyn C. Howlett
Summary: This study aimed to investigate the role of the endocannabinoid system in labor, and found that the protein abundance of CB1 cannabinoid receptor was significantly lower in uterine tissue exposed to labor, supporting the involvement of this system in parturition. These findings contribute to the understanding of the importance of the endocannabinoid system in successful reproduction and highlight the need for further research in this area.
CANNABIS AND CANNABINOID RESEARCH
(2022)
Article
Pharmacology & Pharmacy
Zsolt Safar, Gabor Kecskemeti, Judit Molnar, Anita Kurunczi, Zoltan Szabo, Tamas Janaky, Emese Kis, Peter Krajcsi
Summary: BCRP/ABCG2 is a key factor in the pharmacokinetics of substrate drugs. Membranes from different expression systems show variation in substrate correlation and dynamic range, but good consistency in IC50 values.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2021)
Article
Pharmacology & Pharmacy
Laura Suominen, Noora Sjostedt, Kati-Sisko Vellonen, Mikko Gynther, Seppo Auriola, Heidi Kidron
Summary: Reducing the activity of ABCG2 transporter can lead to increased drug absorption and plasma levels. The Q141K variant of ABCG2 has a clinically significant effect of decreasing protein levels and transport activity. In addition, there are over 500 rare variants of ABCG2, but their functionality is still unknown. This study identified 14 rare variants that have a decreased function phenotype, potentially leading to increased drug exposure.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2023)
Article
Biophysics
M. Gaisberger, J. Fuchs, M. Riedl, S. Edtinger, R. Reischl, G. Grasmann, B. Holzl, F. Landauer, H. Dobias, F. Eckstein, M. Offenbacher, M. Ritter, M. Winklmayr
Summary: The study aimed to investigate the involvement of the endocannabinoid system in a multimodal therapy approach for knee osteoarthritis, finding a significant reduction in knee pain with sustained effect, but no additional benefit from radon therapy. The decrease in pain was accompanied by a significant reduction in AEA plasma levels, suggesting a potential role of the endocannabinoid system in OA pain.
INTERNATIONAL JOURNAL OF BIOMETEOROLOGY
(2021)
Article
Medicine, Research & Experimental
Marc-Olivier Pilon, Gregoire Leclair, Essaid Oussaid, Isabelle St-Jean, Martin Jutras, Marie-Josee Gaulin, Ian Mongrain, David Busseuil, Jean Lucien Rouleau, Jean-Claude Tardif, Marie-Pierre Dube, Simon de Denus
Summary: This study investigated the association between the ABCG2 gene rs2231142 variant and the concentrations of oxypurinol, allopurinol, and allopurinol riboside. The results showed no significant association between the rs2231142 variant and these concentrations, suggesting that ABCG2 might not play a major role in the pharmacokinetics of allopurinol or its metabolites.
CTS-CLINICAL AND TRANSLATIONAL SCIENCE
(2022)
Article
Cell Biology
Meera Manchanda, Emma Leishman, Kishan Sangani, Ali Alamri, Heather B. Bradshaw
Summary: This study investigates how activation of TRPV1 drives regulation of a wider range of lipid signaling molecules, which is time and dose-dependent. The analysis of lipids revealed that capsaicin increases the release of 2-acyl glycerols while decreasing levels of N-acyl ethanolamines. Changes in temperature also result in similar regulation of lipid signaling molecules.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Clinical Neurology
Hajar Mikaeili, Abdella M. Habib, Charlix Wai-Lok Yeung, Sonia Santana-Varela, Ana P. Luiz, Kseniia Panteleeva, Sana Zuberi, Alkyoni Athanasiou-Fragkouli, Henry Houlden, John N. Wood, Andrei L. Okorokov, James J. Cox
Summary: Mikaeili et al. have identified the molecular basis of pain insensitivity associated with FAAH-OUT. This discovery provides insights into the regulation of pain and offers potential for new gene therapy approaches. Chronic pain affects millions of people worldwide and requires urgent treatment options.
Review
Biochemistry & Molecular Biology
Samiksha Kukal, Debleena Guin, Chitra Rawat, Shivangi Bora, Manish Kumar Mishra, Priya Sharma, Priyanka Rani Paul, Neha Kanojia, Gurpreet Kaur Grewal, Shrikant Kukreti, Luciano Saso, Ritushree Kukreti
Summary: ABCG2 is a widely distributed protein in different cell types that plays a crucial role in maintaining cellular homeostasis and protecting tissues against xenobiotic insults, but its expression is influenced by various pathophysiological conditions. Therapeutic interventions should focus on regulating levels of ABCG2 rather than directly inhibiting its function to avoid serious side effects.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Maryam Honarbakhsh, Aaron Ericsson, Guo Zhong, Nina Isoherranen, Chengsheng Zhu, Yana Bromberg, Charlene Van Buiten, Kiana Malta, Laurie Joseph, Harini Sampath, Atreju Lackey, Judith Storch, Costantino Vetriani, Michael L. Chikindas, Paul Breslin, Loredana Quadro
Summary: The deficiency of lecithin:retinol acyltransferase and retinol-binding protein in mice leads to intestinal vitamin A deficiency, compromising gut morphology, barrier function, and microbial composition.
JOURNAL OF LIPID RESEARCH
(2021)