Bile acid composition regulates the manganese transporter Slc30a10 in intestine
Autor: | Enrico Bertaggia, Nicole C. Guilz, Jennifer R. Gamarra, Allison Hung, Niroshan Shanmugarajah, Rebecca A. Haeusler, Sei Higuchi, Tiara R. Ahmad |
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Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
Lithocholic acid medicine.drug_class Ileum Biochemistry Calcitriol receptor Reuptake Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine medicine Organoid Animals Intestinal Mucosa Cation Transport Proteins Molecular Biology 030304 developmental biology Manganese 0303 health sciences Ion Transport 030102 biochemistry & molecular biology Bile acid Chemistry Transporter Cell Biology Organoids 030104 developmental biology medicine.anatomical_structure Nuclear receptor Receptors Calcitriol Lithocholic Acid 030217 neurology & neurosurgery Signal Transduction |
Zdroj: | Journal of Biological Chemistry. 295:12545-12558 |
ISSN: | 0021-9258 |
Popis: | Bile acids (BAs) comprise heterogenous amphipathic cholesterol-derived molecules that carry out physicochemical and signaling functions. A major site of BA action is the terminal ileum, where enterocytes actively reuptake BAs and express high levels of BA-sensitive nuclear receptors. BA pool size and composition are affected by changes in metabolic health, and vice versa. One of several factors that differentiate BAs is the presence of a hydroxyl group on C12 of the steroid ring. 12a-hydroxylated BAs (12HBAs) are altered in multiple disease settings, but the consequences of 12HBA abundance are incompletely understood. We employed mouse primary ileum organoids to investigate the transcriptional effects of varying 12HBA abundance in BA pools. We identifiedSlc30a10as one of the top genes differentially induced by BA pools with varying 12HBA abundance. SLC30A10 is a manganese (Mn) efflux transporter critical for whole-body manganese excretion. We found that BA pools, especially those low in 12HBAs, induce cellular manganese efflux, and thatSlc30a10induction by BA pools is driven primarily by lithocholic acid signaling via the vitamin D receptor. Administration of lithocholic acid or a vitamin D receptor agonist resulted in increasedSlc30a10expression in mouse ileum epithelia. These data demonstrate a previously unknown role for BAs in intestinal control of Mn homeostasis. |
Databáze: | OpenAIRE |
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