Article
Medicine, Research & Experimental
Christine C. Orozco, Mikko Neuvonen, Yi-An Bi, Matthew A. Cerny, Sumathy Mathialagan, Laurie Tylaska, Brian Rago, Chester Costales, Amanda King-Ahmad, Mikko Niemi, A. David Rodrigues
Summary: This study found that sulfated bile acids (BA-S) can potentially serve as clinical biomarkers for OATP1B1/3. The BA-S substrates were observed in OATP1B1, OATP1B3, and NTCP transfected into human embryonic kidney 293 cells, with minimal uptake in other solute carriers (SLCs). Inhibition of BA-S uptake in human hepatocytes was greater with rifampicin (OATP1B1/3 selective inhibitor) than other inhibitors.
MOLECULAR PHARMACEUTICS
(2023)
Article
Chemistry, Medicinal
Katherine D. Lynch, Michelle L. Montonye, Dan-Dan Tian, Tarana Arman, Victoria O. Oyanna, Baron J. Bechtold, Tyler N. Graf, Nicholas H. Oberlies, Mary F. Paine, John D. Clarke
Summary: Silymarin, derived from milk thistle seeds, contains flavonolignans that are substrates for OATPs/Oatps. Research shows that OATPs/Oatps play a role in flavonolignan cellular uptake, and mediate interactions between silymarin and diseases like NASH on drug exposure.
PHYTOTHERAPY RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Yi-Hsueh Lee, Menq-Rong Wu, Jong-Kai Hsiao
Summary: This study confirmed the uptake capability of OATP1B1 for both MR agents and NIR fluorescent dyes, while demonstrating that OATP1B3 exhibits superior ICG uptake capability.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Pharmacology & Pharmacy
Eva Bakos, Orsolya Nemet, Nora Kucsma, Natalia Tokesi, Bruno Stieger, Elisabeth Rushing, Anna-Maria Tokes, Peter Kele, Gabor E. Tusnady, Csilla Ozvegy-Laczka
Summary: In this study, the cloning and functional characterization of a third isoform of OATP3A1, OATP3A1_V3, was described. OATP3A1_V3 showed widespread expression in human organs, with the highest expression in the brain and testis. Immunostaining and functional assays confirmed the expression of OATP3A1_V3 in the human choroid plexus, neurons, and both germ and Sertoli cells of the testis, and identified dehydroepiandrosterone sulfate as a novel OATP3A1 substrate.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Pharmacology & Pharmacy
Jieru Chen, Yuanping Xue, Xiaoyu Shuai, Chunxu Ni, Zihui Fang, Ling Ye, Mei Hong
Summary: This study investigated the inhibitory effects of major components of Triptergium wilfordii Hook. f. (TWHF) on the function of organic anion transporting polypeptide 1B1 (OATP1B1), which plays a crucial role in drug pharmacokinetics. The results showed that the tested TWHF components, especially the alkaloids Wilforine and Wilforgine, significantly inhibited OATP1B1 activity. The co-incubation and pre-incubation of these components had different effects on the function of OATP1B1.
TOXICOLOGY AND APPLIED PHARMACOLOGY
(2022)
Article
Chemistry, Medicinal
Youmna Ali, Tahiatul Shams, Zhengqi Cheng, Yue Li, Chelsea Siu-Wai Chun, Wenying Shu, Xiaofeng Bao, Ling Zhu, Michael Murray, Fanfan Zhou
Summary: This study evaluated the regulatory actions of Wnt inhibitors on human renal Organic anion transporters and Organic anion transporting polypeptides, showing that these inhibitors significantly decrease the activities and membrane expression of multiple transporters. The findings suggest that Wnt inhibitors may have unexpected effects on drug entry into cells.
JOURNAL OF PHARMACEUTICAL SCIENCES
(2021)
Article
Chemistry, Medicinal
Azusa Futatsugi, Yusuke Masuo, Yukio Kato
Summary: The study showed that PBD increased plasma concentrations of four endogenous substrates in rats, but reduced the liver-to-plasma and kidney-to-plasma concentration ratios of HDA and TDA. PBD mainly affected the renal contribution to the disposition of HDA, ODA, and TDA.
JOURNAL OF PHARMACEUTICAL SCIENCES
(2021)
Article
Agriculture, Multidisciplinary
Kengo Sakurai, Jun Abe, Kota Hirasawa, Hayato Takeuchi, Sachiko Kitamoto
Summary: A study examined the metabolic fate of a newly developed herbicide epyrifenacil in rats, finding that it was rapidly metabolized to M1 and mainly excreted through bile. The parent compound was not detected in plasma, tissues, or urine. M1 was predominantly found in the liver, with a significant sex-related difference observed in urinary excretion. The study suggests that organic anion-transporting polypeptide (OATP) may play a role in the active transport of M1 in the liver and kidney.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2021)
Article
Multidisciplinary Sciences
Konstantinos Nakos, Md Noor A. Alam, Megan R. Radler, Ilona A. Kesisova, Changsong Yang, Joshua Okletey, Meagan R. Tomasso, Shae B. Padrick, Tatyana M. Svitkina, Elias T. Spiliotis
Summary: Cellular morphogenesis and processes such as cell division and migration require the coordination of the microtubule and actin cytoskeletons. This study shows that septins mediate microtubule-actin crosstalk by coupling actin polymerization to microtubule lattices.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biology
Morgan L. Pimm, Xinbei Liu, Farzana Tuli, Jennifer Heritz, Ashley Lojko, Jessica L. Henty-Ridilla
Summary: PFN1 is an important protein that regulates actin and microtubule assembly, affecting cell division, motility, and morphology. Two genetically encoded versions of tagged PFN1 have been developed and shown to behave identically to the tag-free protein. These tagged PFN1s are reliable tools for studying the interactions of PFN1 with actin or microtubules.
Article
Multidisciplinary Sciences
Lewis Hun, Naoki Okamoto, Eisuke Imura, Roilea Maxson, Riyan Bittar, Naoki Yamanaka
Summary: The primary insect steroid hormone ecdysone requires a membrane transporter to enter its target cells. Although an organic anion-transporting polypeptide (OATP) named Ecdysone Importer (EcI) serves this role in the fruit fly Drosophila melanogaster and most likely in other arthropod species, this highly conserved transporter is apparently missing in mosquitoes. Here we report three additional OATPs that facilitate cellular incorporation of ecdysone in Drosophila and the yellow fever mosquito Aedes aegypti. These additional ecdysone importers (EcI-2, -3, and -4) are dispensable for development and reproduction in Drosophila, consistent with the predominant role of Ed. In contrast, in Aedes, EcI-2 is indispensable for ecdysone-mediated development, whereas EcI-4 is critical for vitellogenesis induced by ecdysone in adult females. Altogether, our results indicate unique and essential functions of these additional ecdysone importers in mosquito development and reproduction, making them attractive molecular targets for species- and stage-specific control of ecdysone signaling in mosquitoes.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemistry & Molecular Biology
Santosh Kumar Adla, Arun Kumar Tonduru, Thales Kronenberger, Eva Kudova, Antti Poso, Kristiina M. Huttunen
Summary: In this study, synthetic neurosteroids were delivered into MCF-7 cells via OATPs to investigate structural components necessary for cellular uptake and understand brain drug delivery. The research identified key structural features that improve the affinity of neurosteroids and interact with specific amino acids, providing insights for potential drug delivery strategies across the blood-brain barrier.
Article
Plant Sciences
Ruifeng Liang, Wenjing Ge, Bingjie Li, Weifeng Cui, Xiaofan Ma, Yuying Pan, Gengsheng Li
Summary: The study showed that evodiamine reduced the systemic exposure of pravastatin in NASH rats by enhancing the uptake and distribution in the liver. This was achieved by up-regulating the expression of OATPs. Additionally, evodiamine also decreased the levels of pro-inflammatory cytokines in NASH rats.
PHARMACEUTICAL BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Nikolas Hundt, Daniel Cole, Max F. Hantke, Jack J. Miller, Weston B. Struwe, Philipp Kukura
Summary: This study uses mass photometry to investigate the polymerization process of actin and finds that the traditional nucleation-based models cannot explain the observed distribution of actin oligomers. Instead, the key step of filament formation is a slow transition between different states of an actin filament mediated by cation exchange or ATP hydrolysis. These findings have important implications for understanding the mechanism of actin nucleation and studying protein assembly at the molecular level.
Article
Multidisciplinary Sciences
Kaitlin Katsura, Yukiko Nakano, Yan Zhang, Rozana Shemirani, Wu Li, Pamela Den Besten
Summary: Tooth enamel formation is a complex process regulated by multiple differentiation stages and key genes. WDR72, a gene found in various organs, including the teeth, has been discovered to cause enamel defects when deleted or mutated. Unlike other enamel regulation genes, WDR72 functions intracellularly and regulates endocytosis of proteins. The study suggests that WDR72 plays a role in microtubule assembly and directs membrane mobilization and vesicle transport, providing insights into tissue mineralization.
SCIENTIFIC REPORTS
(2022)