期刊
CNS NEUROSCIENCE & THERAPEUTICS
卷 22, 期 9, 页码 789-798出版社
WILEY
DOI: 10.1111/cns.12585
关键词
alpha-Amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor; GluR1; Hydrogen sulfide; Protein kinases; Protein phosphatase type 2A; Sulfhydration
资金
- National Basic Research Program of China (the 973 Program) [2013CB531303, 2014CB744601]
- National Science and Technology Major Projects for New Drugs Innovation and Development [2012ZX09103-101-045]
- National Major Scientific Instrument and Equipment Development Projects [2013YQ03092306]
- PCSIRT [IRT13016]
AimsHydrogen sulfide (H2S) has been widely accepted as a gas neuromodulator to regulate synaptic function. Herein, we set out to determine the effect of H2S on -amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor (AMPAR) and its mechanism. MethodsBS(3) protein cross-linking, Western blot, patch clamp, and biotin-switch assay. ResultsBath application of H2S donor NaHS (50 and 100 M) rapidly promoted surface insertion of hippocampal AMPAR GluR1 subunit. This effect can be abolished by dithiothreitol (DTT) and mimicked by Na2S4, 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. H2S increased S-sulfhydration of protein phosphatase type 2A (PP2A), which may be partially involved in the activation of signal pathways. ConclusionOur data suggest that H2S promotes surface insertion of AMPARs via phosphorylation of GluR1, which depends on a sulfhydration-mediated mechanism.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据