title: Chronic Nicotine Exposure In Vivo and In Vitro Inhibits Vitamin B1 (Thiamin) Uptake by Pancreatic Acinar Cells.
abstract: Thiamin (vitamin B1), a member of the water-soluble family of vitamins, is essential for normal cellular functions; its deficiency results in oxidative stress and mitochondrial dysfunction. Pancreatic acinar cells (PAC) obtain thiamin from the circulation using a specific carrier-mediated process mediated by both thiamin transporters -1 and -2 (THTR-1 and THTR-2; encoded by the SLC19A2 and SLC19A3 genes, respectively). The aim of the current study was to examine the effect of chronic exposure of mouse PAC in vivo and human PAC in vitro to nicotine (a major component of cigarette smoke that has been implicated in pancreatic diseases) on thiamin uptake and to delineate the mechanism involved. The results showed that chronic exposure of mice to nicotine significantly inhibits thiamin uptake in murine PAC, and that this inhibition is associated with a marked decrease in expression of THTR-1 and THTR-2 at the protein, mRNA and hnRNAs level. Furthermore, expression of the important thiamin-metabolizing enzyme, thiamin pyrophosphokinase (TPKase), was significantly reduced in PAC of mice exposed to nicotine. Similarly, chronic exposure of cultured human PAC to nicotine (0.5 μM, 48 h) significantly inhibited thiamin uptake, which was also associated with a decrease in expression of THTR-1 and THTR-2 proteins and mRNAs. This study demonstrates that chronic exposure of PAC to nicotine impairs the physiology and the molecular biology of the thiamin uptake process. Furthermore, the study suggests that the effect is, in part, mediated through transcriptional mechanism(s) affecting the SLC19A2 and SLC19A3 genes.
authors.affiliation: Department of Medical Research, VA Medical Center, Long Beach, California, United States of America.|Departments of Medicine and Physiology/Biophysics, University of California Irvine, Irvine, California, United States of America.
authors.forename: Padmanabhan
authors.initials: P
authors.lastname: Srinivasan
authors.affiliation: Section of Digestive Diseases, Department of Internal Medicine, School of Medicine, Yale University, New Haven, Connecticut, United States of America.
authors.forename: Edwin C
authors.initials: EC
authors.lastname: Thrower
authors.affiliation: Clinical Islet Cell Laboratory, Department of Surgery, Cardiovascular Innovation Institute, University of Louisville, Louisville, Kentucky, United States of America.
authors.forename: Gopalakrishnan
authors.initials: G
authors.lastname: Loganathan
authors.affiliation: Clinical Islet Cell Laboratory, Department of Surgery, Cardiovascular Innovation Institute, University of Louisville, Louisville, Kentucky, United States of America.
authors.forename: A N
authors.initials: AN
authors.lastname: Balamurugan
authors.affiliation: Department of Medical Research, VA Medical Center, Long Beach, California, United States of America.|Departments of Medicine and Physiology/Biophysics, University of California Irvine, Irvine, California, United States of America.
authors.forename: Veedamali S
authors.initials: VS
authors.lastname: Subramanian
authors.affiliation: Section of Digestive Diseases, Department of Internal Medicine, Yale University, New Haven, Connecticut.|Veterans Affairs Healthcare System, West Haven, Connecticut, United States of America.
authors.forename: Fred S
authors.initials: FS
authors.lastname: Gorelick
authors.affiliation: Department of Medical Research, VA Medical Center, Long Beach, California, United States of America.|Departments of Medicine and Physiology/Biophysics, University of California Irvine, Irvine, California, United States of America.
authors.forename: Hamid M
authors.initials: HM
authors.lastname: Said
mesh_terms: D061354:Acinar Cells / Q000187:drug effects* / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D006801:Humans; D026901:Membrane Transport Proteins / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D008875:Middle Aged; D009538:Nicotine / Q000494:pharmacology*; D013836:Thiamin Pyrophosphokinase / Q000378:metabolism; D013831:Thiamine / Q000378:metabolism*; D055815:Young Adult
chemical_list: D026901:Membrane Transport Proteins; C120043:SLC19A2 protein, human; C492291:SLC19A3 protein, human; D009538:Nicotine; D013836:Thiamin Pyrophosphokinase; D013831:Thiamine