Journal article
ADAR2-dependent RNA editing of GluR2 is involved in thiamine deficiency-induced alteration of calcium dynamics
Molecular neurodegeneration, Vol.5(1), pp.54-54
2010
DOI: 10.1186/1750-1326-5-54
PMCID: PMC3006372
PMID: 21110885
Abstract
Background: Thiamine (vitamin B1) deficiency (TD) causes mild impairment of oxidative metabolism and region-selective neuronal loss in the central nervous system (CNS). TD in animals has been used to model aging-associated neurodegeneration in the brain. The mechanisms of TD-induced neuron death are complex, and it is likely multiple mechanisms interplay and contribute to the action of TD. In this study, we demonstrated that TD significantly increased intracellular calcium concentrations [Ca2+]i in cultured cortical neurons.
Results: TD drastically potentiated AMPA-triggered calcium influx and inhibited pre-mRNA editing of GluR2, a Ca2+-permeable subtype of AMPA receptors. The Ca2+ permeability of GluR2 is regulated by RNA editing at the Q/R site. Edited GluR2 (R) subunits form Ca2+-impermeable channels, whereas unedited GluR2 (Q) channels are permeable to Ca2+ flow. TD inhibited Q/R editing of GluR2 and increased the ratio of unedited GluR2. The Q/R editing of GluR2 is mediated by adenosine deaminase acting on RNA 2 (ADAR2). TD selectively decreased ADAR2 expression and its self-editing ability without affecting ADAR1 in cultured neurons and in the brain tissue. Over-expression of ADAR2 reduced AMPA-mediated rise of [Ca2+]i and protected cortical neurons against TD-induced cytotoxicity, whereas down-regulation of ADAR2 increased AMPA-elicited Ca2+ influx and exacerbated TD-induced death of cortical neurons.
Conclusions: Our findings suggest that TD-induced neuronal damage may be mediated by the modulation of ADAR2-dependent RNA Editing of GluR2.
Details
- Title: Subtitle
- ADAR2-dependent RNA editing of GluR2 is involved in thiamine deficiency-induced alteration of calcium dynamics
- Creators
- Shuchen Lee - Chinese Academy of SciencesGuang Yang - Chinese Academy of SciencesYue Yong - Chinese Academy of SciencesYing Liu - Chinese Academy of SciencesLiyun Zhao - Chinese Academy of SciencesJing Xu - Shanghai Pudong New Area Gongli HospitalXiaomin Zhang - Chinese Academy of SciencesYanjie Wan - Department of Anesthesiology, Gongli Hospital, Pudong, ChinaChun Feng - Chinese Academy of SciencesZhiqin Fan - Chinese Academy of SciencesYong Liu - Chinese Academy of SciencesJia Luo - Chinese Academy of SciencesZun-Ji Ke - Shanghai Institutes for Biological Sciences
- Resource Type
- Journal article
- Publication Details
- Molecular neurodegeneration, Vol.5(1), pp.54-54
- DOI
- 10.1186/1750-1326-5-54
- PMID
- 21110885
- PMCID
- PMC3006372
- NLM abbreviation
- Mol Neurodegener
- ISSN
- 1750-1326
- eISSN
- 1750-1326
- Publisher
- BioMed Central
- Language
- English
- Date published
- 2010
- Academic Unit
- Pathology
- Record Identifier
- 9984186640802771
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