title: Protein cysteine S-nitrosylation inhibits vesicular uptake of neurotransmitters.
abstract: Previous studies have shown that nitric oxide can induce cysteine S-nitrosylation of total protein in synaptosomes, suggesting that nitric oxide may contribute to the regulation of synaptic protein function. Vesicular neurotransmitter transporters pack neurotransmitters into synaptic vesicles and play an important role in neurotransmission. In the central nervous system, vesicular monoamine transporter 2 (VMAT2) is responsible for the uptake of monoamines, vesicular acetylcholine transporter (VAChT) is responsible for the uptake of acetylcholine, while vesicular glutamate transporters 1 and 2 (VGLUT1 and VGLUT2) are responsible for the uptake of glutamate. The purpose of this study was to investigate the role of cysteine S-nitrosylation in the regulation of these vesicular neurotransmitter transporters. Using the biotin switch assay followed by avidin precipitation and immunoblotting we found that the nitric oxide donor nitrosoglutathione (GSNO) not only increased total cysteine S-nitrosylation, but also increased cysteine S-nitrosylation of VMAT2, VAChT, VGLUT1 and VGLUT2 in the mouse brain. Further, GSNO also decreased the vesicular uptake of [(3)H]dopamine, [(3)H]acetylcholine and [(3)H]glutamate. Our studies suggest that the cysteine S-nitrosylation may play an important role in the regulation of vesicular neurotransmitter transport.
authors.affiliation: Kleysen Institute for Advanced Medicine, Health Sciences Centre, Winnipeg, Canada; Department of Pharmacology and Therapeutics, University of Manitoba, Winnipeg, Canada.
authors.forename: Y
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: Z
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: T
authors.initials: T
authors.lastname: Leylek
authors.affiliation: Kleysen Institute for Advanced Medicine, Health Sciences Centre, Winnipeg, Canada; Department of Pharmacology and Therapeutics, University of Manitoba, Winnipeg, Canada.
authors.forename: H
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: Y
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Kleysen Institute for Advanced Medicine, Health Sciences Centre, Winnipeg, Canada; Department of Pharmacology and Therapeutics, University of Manitoba, Winnipeg, Canada.
authors.forename: F E
authors.initials: FE
authors.lastname: Parkinson
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. Electronic address: jun-feng.wang@umanitoba.ca.
authors.forename: J-F
authors.initials: JF
authors.lastname: Wang
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D026422:S-Nitrosoglutathione / Q000031:analogs & derivatives / Q000494:pharmacology; D014316:Tritium; D050494:Vesicular Acetylcholine Transport Proteins / Q000378:metabolism*; D050598:Vesicular Glutamate Transport Protein 1 / Q000378:metabolism*; D050599:Vesicular Glutamate Transport Protein 2 / Q000378:metabolism*; D050493:Vesicular Monoamine Transport Proteins / Q000378:metabolism*
chemical_list: D020030:Nitric Oxide Donors; C493477:Slc17a6 protein, mouse; C493465:Slc17a7 protein, mouse; C493453:Slc18a2 protein, mouse; C493460:Slc18a3 protein, mouse; D050494:Vesicular Acetylcholine Transport Proteins; D050598:Vesicular Glutamate Transport Protein 1; D050599:Vesicular Glutamate Transport Protein 2; D050493:Vesicular Monoamine Transport Proteins; D014316:Tritium; D009569:Nitric Oxide; D018698:Glutamic Acid; D026422:S-Nitrosoglutathione; D000109:Acetylcholine; D004298:Dopamine
keywords: neurotransmitter uptake; nitric oxide; nitrosylation; vesicular neurotransmitter transporters