title: Dexmedetomidine increases acetylation level of histone through ERK1/2 pathway in dopamine neuron.
abstract: Dexmedetomidine is a highly selective α2-adrenoceptor agonist with sedation, anesthetic sparing, analgesia, sympatholytic, and neuroprotective properties. This study evaluated neuroprotective effects of dexmedetomidine on dopamine neurons correlated to histone acetylation via extracellular signal-regulated protein kinase 1 and 2 (ERK1/2) pathway. Animals were randomly assigned to four groups and treatments were given as onetime doses: dimethyl sulfoxide (DMSO; n = 6), dexmedetomidine 1 mg/kg ( n = 6), 10 mg/kg ( n = 6), and 100 mg/kg ( n = 6). Acetylation histone protein levels and ERK protein levels in rats dopamine neuron from striatum were determined by Western blotting after various doses of dexmedetomidine (1, 10, and 100 mg/kg) treatments. The messenger RNA expression related to signal transduction coupled to 5-hydroxytryptamine receptor (5-HTR) in striatum was assessed by quantitative real-time polymerase chain reaction (qRT-PCR) analysis. Dexmedetomidine administration increased expression of ERK1/2 phosphorylation and histones H3 acetylation. PD098059, an inhibitor of pERK1/2, almost completely blocked dexmedetomidine-induced histones H3 acetylation. In addition, bioinformatics analysis in combination with qRT-PCR demonstrated that dexmedetomidine could regulate the genes that are related to signal transduction coupled to 5-HTR via α2-adrenoceptor. Our results define dexmedetomidine as a modulator of histones H3 acetylation via ERK1/2 signaling pathway in dopamine neuron from striatum, which may provide clues for the mechanism underlying the neuroprotective effects of dexmedetomidine.
authors.affiliation: 1 Department of Anesthesiology, Huzhou Central Hospital, Huzhou, Zhejiang, People's Republic of China.
authors.forename: S-P
authors.initials: SP
authors.lastname: Hu
authors.affiliation: 2 Department of Orthopedics, Huzhou Central Hospital, Huzhou, Zhejiang, People's Republic of China.
authors.forename: J-J
authors.initials: JJ
authors.lastname: Zhao
authors.affiliation: 1 Department of Anesthesiology, Huzhou Central Hospital, Huzhou, Zhejiang, People's Republic of China.
authors.forename: W-X
authors.initials: WX
authors.lastname: Wang
authors.affiliation: 1 Department of Anesthesiology, Huzhou Central Hospital, Huzhou, Zhejiang, People's Republic of China.
authors.forename: Y
authors.initials: Y
authors.lastname: Liu
authors.affiliation: 1 Department of Anesthesiology, Huzhou Central Hospital, Huzhou, Zhejiang, People's Republic of China.
authors.forename: H-F
authors.initials: HF
authors.lastname: Wu
authors.affiliation: 1 Department of Anesthesiology, Huzhou Central Hospital, Huzhou, Zhejiang, People's Republic of China.
authors.forename: C
authors.initials: C
authors.lastname: Chen
authors.affiliation: 1 Department of Anesthesiology, Huzhou Central Hospital, Huzhou, Zhejiang, People's Republic of China.
authors.forename: L
authors.initials: L
authors.lastname: Yu
authors.affiliation: 1 Department of Anesthesiology, Huzhou Central Hospital, Huzhou, Zhejiang, People's Republic of China.
authors.forename: J-B
authors.initials: JB
authors.lastname: Gui
mesh_terms: D000107:Acetylation; D058647:Adrenergic alpha-2 Receptor Agonists / Q000494:pharmacology; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology; D000818:Animals; D003342:Corpus Striatum / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D020927:Dexmedetomidine / Q000494:pharmacology*; D059290:Dopaminergic Neurons / Q000187:drug effects* / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005419:Flavonoids / Q000494:pharmacology; D006657:Histones / Q000378:metabolism*; D006993:Hypnotics and Sedatives / Q000494:pharmacology; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D020411:Oligonucleotide Array Sequence Analysis; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000235:genetics
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D018712:Analgesics, Non-Narcotic; D005419:Flavonoids; D006657:Histones; D006993:Hypnotics and Sedatives; D018696:Neuroprotective Agents; D047428:Protein Kinase Inhibitors; D011985:Receptors, Serotonin; D020927:Dexmedetomidine; D048049:Extracellular Signal-Regulated MAP Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one
keywords: Dexmedetomidine; Htr signal; histone acetylation; neuroprotection