1. Dexmedetomidine increases acetylation level of histone through ERK1/2 pathway in dopamine neuron
- Author
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Yu L, Hu Sp, Chen C, Zhao Jj, Yong Liu, Wang Wx, Gui Jb, and Wu Hf
- Subjects
Male ,0301 basic medicine ,Agonist ,MAPK/ERK pathway ,medicine.drug_class ,Health, Toxicology and Mutagenesis ,Pharmacology ,Toxicology ,Histones ,Rats, Sprague-Dawley ,03 medical and health sciences ,0302 clinical medicine ,Dopamine ,Adrenergic alpha-2 Receptor Agonists ,medicine ,Animals ,Hypnotics and Sedatives ,Dexmedetomidine ,Extracellular Signal-Regulated MAP Kinases ,Protein kinase A ,Protein Kinase Inhibitors ,Oligonucleotide Array Sequence Analysis ,Flavonoids ,biology ,Chemistry ,Dopaminergic Neurons ,Acetylation ,General Medicine ,Analgesics, Non-Narcotic ,Corpus Striatum ,Neuroprotective Agents ,030104 developmental biology ,Histone ,Receptors, Serotonin ,biology.protein ,Signal transduction ,030217 neurology & neurosurgery ,medicine.drug - 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.
- Published
- 2016