title: Lipopolysaccharide inhibits colonic biotin uptake via interference with membrane expression of its transporter: a role for a casein kinase 2-mediated pathway.
abstract: Biotin (vitamin B7), an essential micronutrient for normal cellular functions, is obtained from both dietary sources as well as gut microbiota. Absorption of biotin in both the small and large intestine is via a carrier-mediated process that involves the sodium-dependent multivitamin transporter (SMVT). Although different physiological and molecular aspects of intestinal biotin uptake have been delineated, nothing is known about the effect of LPS on the process. We addressed this issue using in vitro (human colonic epithelial NCM460 cells) and in vivo (mice) models of LPS exposure. Treating NCM460 cells with LPS was found to lead to a significant inhibition in carrier-mediated biotin uptake. Similarly, administration of LPS to mice led to a significant inhibition in biotin uptake by native colonic tissue. Although no changes in total cellular SMVT protein and mRNA levels were observed, LPS caused a decrease in the fraction of SMVT expressed at the cell surface. A role for casein kinase 2 (CK2) (whose activity was also inhibited by LPS) in mediating the endotoxin effects on biotin uptake and on membrane expression of SMVT was suggested by findings that specific inhibitors of CK2, as well as mutating the putative CK2 phosphorylation site (Thr78Ala) in the SMVT protein, led to inhibition in biotin uptake and membrane expression of SMVT. This study shows for the first time that LPS inhibits colonic biotin uptake via decreasing membrane expression of its transporter and that these effects likely involve a CK2-mediated pathway.
authors.affiliation: Departments of Medicine and Physiology/Biophysics, University of California, Irvine, California; and Department of Medical Research, VA Medical Center, Long Beach, California.
authors.forename: Ram
authors.initials: R
authors.lastname: Lakhan
authors.affiliation: Departments of Medicine and Physiology/Biophysics, University of California, Irvine, California; and Department of Medical Research, VA Medical Center, Long Beach, California hmsaid@uci.edu.
authors.forename: Hamid M
authors.initials: HM
authors.lastname: Said
mesh_terms: D000818:Animals; D001710:Biotin / Q000493:pharmacokinetics*; D047390:Casein Kinase II / Q000378:metabolism*; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism*; D003106:Colon / Q000000981:diagnostic imaging / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects; D006801:Humans; D007408:Intestinal Absorption / Q000187:drug effects / Q000502:physiology; D008070:Lipopolysaccharides / Q000008:administration & dosage*; D051379:Mice; D015398:Signal Transduction / Q000187:drug effects; D013045:Species Specificity; D027981:Symporters / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D008070:Lipopolysaccharides; D027981:Symporters; C119981:biotin transporter; D001710:Biotin; D047390:Casein Kinase II
keywords: LPS; biotin; transport colon