title: Long non-coding RNA C2dat1 regulates CaMKIIδ expression to promote neuronal survival through the NF-κB signaling pathway following cerebral ischemia.
abstract: Increasing evidence has demonstrated a significant role of long non-coding RNAs (lncRNAs) in diverse biological processes. However, their functions in cerebral ischemia remain largely unknown. Through an lncRNA array analysis in a rat model of focal cerebral ischemia/reperfusion (I/R), we have identified CAMK2D-associated transcript 1 (C2dat1) as a novel I/R-induced lncRNA that regulated the expression of CaMKIIδ in murine models of focal cerebral ischemia. C2dat1 mRNA was upregulated in a time-dependent manner in mouse cortical penumbra after focal ischemic brain injury, which was accompanied by increased expression of CaMKIIδ at transcript and protein levels. The expression patterns of C2dat1 and CAMK2D were confirmed in mouse Neuro-2a cells in response to in vitro ischemia (oxygen-glucose deprivation/reoxygenation, OGD/R). Knockdown of C2dat1 resulted in a significant blockade of CaMKIIδ expression, and potentiated OGD/R-induced cell death. Mechanistically, reduced CaMKIIδ expression upon silencing C2dat1 inhibited OGD/R-induced activation of the NF-κB signaling pathway. Further analysis showed that the downregulation of IKKα and IKKβ expression and phosphorylation, and subsequent inhibition of IκBα degradation accounted for the inhibition of the NF-κB signaling activity caused by silencing C2dat1. In summary, we discovered a novel I/R-induced lncRNA C2dat1 that modulates the expression of CaMKIIδ to impact neuronal survival, and may be a potential target for therapeutic intervention of ischemic brain injury.
authors.affiliation: Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.|Department of Pharmacy, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Xu
authors.affiliation: Department of Cell Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.
authors.forename: F
authors.initials: F
authors.lastname: Deng
authors.affiliation: Department of Cell Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Xing
authors.affiliation: Department of Pharmacy, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Wu
authors.affiliation: Department of Pharmacy, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: B
authors.initials: B
authors.lastname: Cen
authors.affiliation: Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
authors.forename: S
authors.initials: S
authors.lastname: Xu
authors.affiliation: Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
authors.forename: Z
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: Department of Neurology, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: R
authors.initials: R
authors.lastname: Nepomuceno
authors.affiliation: Department of Neurology, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: M I H
authors.initials: MI
authors.lastname: Bhuiyan
authors.affiliation: Department of Neurology, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: D
authors.initials: D
authors.lastname: Sun
authors.affiliation: Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
authors.forename: Q J
authors.initials: QJ
authors.lastname: Wang
authors.affiliation: Department of Pharmacy, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: A
authors.initials: A
authors.lastname: Ji
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002545:Brain Ischemia / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology; D051550:I-kappa B Kinase / Q000378:metabolism; D020244:Infarction, Middle Cerebral Artery; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D010100:Oxygen / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D034622:RNA Interference; D062085:RNA, Long Noncoding / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D016328:NF-kappa B; D062085:RNA, Long Noncoding; D051550:I-kappa B Kinase; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; C517673:Camk2d protein, mouse; D005947:Glucose; D010100:Oxygen