title: Hydrogen Sulfide Promotes Surface Insertion of Hippocampal AMPA Receptor GluR1 Subunit via Phosphorylating at Serine-831/Serine-845 Sites Through a Sulfhydration-Dependent Mechanism.
abstract: Hydrogen sulfide (H2 S) has been widely accepted as a gas neuromodulator to regulate synaptic function. Herein, we set out to determine the effect of H2 S on α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor (AMPAR) and its mechanism.
  
  
  
  BS(3) protein cross-linking, Western blot, patch clamp, and biotin-switch assay.
  
  
  
  Bath application of H2 S donor NaHS (50 and 100 μM) rapidly promoted surface insertion of hippocampal AMPAR GluR1 subunit. This effect can be abolished by dithiothreitol (DTT) and mimicked by Na2 S4 , indicating that a sulfhydration-dependent mechanism may be involved. NaHS increased APMAR-mediated EPSC and led to an elevation of GluR2-lacking AMPAR content. Notably, NaHS did not increase the sulfhydration of AMPAR subunits, but it significantly increased the phosphorylation of GluR1 at serine-831 and serine-845 sites. Postsynaptic signal pathways that control GluR1 phosphorylation, such as protein kinase A (PKA), protein kinase C, and calcium/calmodulin-dependent protein kinases II (CaMKII), were sulfhydrated, activated by NaHS, and these effects can be occluded by DTT. H2 S increased S-sulfhydration of protein phosphatase type 2A (PP2A), which may be partially involved in the activation of signal pathways.
  
  
  
  Our data suggest that H2 S promotes surface insertion of AMPARs via phosphorylation of GluR1, which depends on a sulfhydration-mediated mechanism.
authors.affiliation: Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Yuan-Long
authors.initials: YL
authors.lastname: Li
authors.affiliation: Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Hai
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Luo
authors.affiliation: Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.|Key Laboratory of Neurological Diseases (HUST), Ministry of Education of China, Wuhan, Hubei, China.|The Key Laboratory for Drug Target Researches and Pharmacodynamic Evaluation of Hubei Province, Wuhan, Hubei, China.|Laboratory of Neuropsychiatric Diseases, The Institute of Brain Research, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Li-Hong
authors.initials: LH
authors.lastname: Long
authors.affiliation: Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.|Key Laboratory of Neurological Diseases (HUST), Ministry of Education of China, Wuhan, Hubei, China.|The Key Laboratory for Drug Target Researches and Pharmacodynamic Evaluation of Hubei Province, Wuhan, Hubei, China.|Laboratory of Neuropsychiatric Diseases, The Institute of Brain Research, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Zhuang-Li
authors.initials: ZL
authors.lastname: Hu
authors.affiliation: Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.|Key Laboratory of Neurological Diseases (HUST), Ministry of Education of China, Wuhan, Hubei, China.|The Key Laboratory for Drug Target Researches and Pharmacodynamic Evaluation of Hubei Province, Wuhan, Hubei, China.|Laboratory of Neuropsychiatric Diseases, The Institute of Brain Research, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Jian-Guo
authors.initials: JG
authors.lastname: Chen
authors.affiliation: Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.|Key Laboratory of Neurological Diseases (HUST), Ministry of Education of China, Wuhan, Hubei, China.|The Key Laboratory for Drug Target Researches and Pharmacodynamic Evaluation of Hubei Province, Wuhan, Hubei, China.|Laboratory of Neuropsychiatric Diseases, The Institute of Brain Research, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.|Key Laboratory of Neurological Diseases (HUST), Ministry of Education of China, Wuhan, Hubei, China.|The Key Laboratory for Drug Target Researches and Pharmacodynamic Evaluation of Hubei Province, Wuhan, Hubei, China.|Laboratory of Neuropsychiatric Diseases, The Institute of Brain Research, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Peng-Fei
authors.initials: PF
authors.lastname: Wu
mesh_terms: D000818:Animals; D001710:Biotin / Q000378:metabolism; D004229:Dithiothreitol / Q000494:pharmacology; D004558:Electric Stimulation; D004789:Enzyme Activation / Q000187:drug effects; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006862:Hydrogen Sulfide / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D018408:Patch-Clamp Techniques; D010766:Phosphorylation / Q000187:drug effects; D011494:Protein Kinases / Q000378:metabolism; D054648:Protein Phosphatase 2 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000235:genetics / Q000378:metabolism*; D012694:Serine / Q000378:metabolism*; D013440:Sulfides / Q000494:pharmacology
chemical_list: D001710:Biotin; D004229:Dithiothreitol; D006862:Hydrogen Sulfide; D011494:Protein Kinases; D054648:Protein Phosphatase 2; D018091:Receptors, AMPA; D012694:Serine; D013440:Sulfides; C025451:sodium bisulfide
keywords: GluR1; Hydrogen sulfide; Protein kinases; Protein phosphatase type 2A; Sulfhydration; α-Amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor