title: Nitrosylation of Vesicular Transporters in Brain of Amyloid Precursor Protein/Presenilin 1 Double Transgenic Mice.
abstract: Nitric oxide can attack thiol groups of cysteine residues in proteins and induce protein cysteine S-nitrosylation. Cholinergic and glutamatergic systems are dysregulated in Alzheimer's disease. Vesicular acetylcholine transporter (VAChT) and vesicular glutamate transporter 1 (VGLUT1) are important in packaging acetylcholine and glutamate into vesicles, which is an important step for neurotransmission. Previously we found that VAChT and VGLUT1 can be nitrosylated and that S-nitrosylation of these transporters inhibits vesicular uptake of acetylcholine and glutamate. To understand the role of VAChT and VGLUT1 nitrosylation in the pathophysiological development of Alzheimer's disease, we analyzed nitrosylation of VAChT and VGLUT1 in brain of amyloid precursor protein (APP) and presenilin 1 (PS1) double transgenic mice, an animal model for Alzheimer's disease. Using a Morris water maze test, we found that 9- and 12-month-old APP/PS1 mice showed memory deficit, compared to wild type mice. We further found that total protein nitrosylation was increased in frontal cortex and hippocampus of 9- and 12-month-old APP/PS1 mice. Although nitrosylation of VAChT and VGLUT1 was not changed in hippocampus of 9- and 12-month-old APP/PS1 mice, nitrosylation of VAChT and VGLUT1 was significantly increased in frontal cortex of APP/PS1 mice at these ages. We also found that nitrosylation of VAChT and VGLUT1 was increased in hippocampus (but not frontal cortex) of 3-month-old APP/PS1 mice. These findings suggest that nitrosylation of VAChT and VGLUT1 may be associated with dysfunctional acetylcholinergic and glutamatergic neurotransmission in Alzheimer's disease.
authors.affiliation: Kleysen Institute for Advanced Medicine, Health Sciences Centre, Winnipeg, Canada.|Department of Pharmacology and Therapeutics, University of Manitoba, Winnipeg, Canada.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Kleysen Institute for Advanced Medicine, Health Sciences Centre, Winnipeg, Canada.|Department of Pharmacology and Therapeutics, University of Manitoba, Winnipeg, Canada.
authors.forename: Zhu
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: Kleysen Institute for Advanced Medicine, Health Sciences Centre, Winnipeg, Canada.|Department of Pharmacology and Therapeutics, University of Manitoba, Winnipeg, Canada.
authors.forename: Hua
authors.initials: H
authors.lastname: Tan
authors.affiliation: Kleysen Institute for Advanced Medicine, Health Sciences Centre, Winnipeg, Canada.|Department of Pharmacology and Therapeutics, University of Manitoba, Winnipeg, Canada.
authors.forename: Shenghua
authors.initials: S
authors.lastname: Zhu
authors.affiliation: Kleysen Institute for Advanced Medicine, Health Sciences Centre, Winnipeg, Canada.|Department of Pharmacology and Therapeutics, University of Manitoba, Winnipeg, Canada.
authors.forename: Yiran
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Kleysen Institute for Advanced Medicine, Health Sciences Centre, Winnipeg, Canada.|Department of Pharmacology and Therapeutics, University of Manitoba, Winnipeg, Canada.
authors.forename: Yingxia
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Psychiatry, University of Alberta, Edmonton, Canada.
authors.forename: Xin-Min
authors.initials: XM
authors.lastname: Li
authors.affiliation: Kleysen Institute for Advanced Medicine, Health Sciences Centre, Winnipeg, Canada.|Department of Pharmacology and Therapeutics, University of Manitoba, Winnipeg, Canada.|Department of Psychiatry, University of Manitoba, Winnipeg, Canada.
authors.forename: Jun-Feng
authors.initials: JF
authors.lastname: Wang
mesh_terms: D000367:Age Factors; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism / Q000494:pharmacology; D016564:Amyloid beta-Protein Precursor / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002461:Cell Line, Transformed; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D006801:Humans; D018782:Maze Learning; D051379:Mice; D008822:Mice, Transgenic; D009569:Nitric Oxide / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism / Q000494:pharmacology; D053764:Presenilin-1 / Q000235:genetics* / Q000378:metabolism; D014162:Transfection; D050494:Vesicular Acetylcholine Transport Proteins / Q000378:metabolism; D050598:Vesicular Glutamate Transport Protein 1 / Q000378:metabolism; D033921:Vesicular Transport Proteins / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D010446:Peptide Fragments; D053764:Presenilin-1; D050494:Vesicular Acetylcholine Transport Proteins; D050598:Vesicular Glutamate Transport Protein 1; D033921:Vesicular Transport Proteins; C075222:amyloid beta-protein (1-42); D009569:Nitric Oxide
keywords: Alzheimer’s disease; oxidative stress; protein nitrosylation; vesicular acetylcholine transporter; vesicular glutamate transporter