RGD Reference Report - Kdm6A Protects Against Hypoxia-Induced Cardiomyocyte Apoptosis via H3K27me3 Demethylation of Ncx Gene. - Rat Genome Database

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Kdm6A Protects Against Hypoxia-Induced Cardiomyocyte Apoptosis via H3K27me3 Demethylation of Ncx Gene.

Authors: Li, Yu  Quan, Xin  Li, Xialing  Pan, Yu  Zhang, Tao  Liang, Zhuo  Wang, Yunlong 
Citation: Li Y, etal., J Cardiovasc Transl Res. 2019 Oct;12(5):488-495. doi: 10.1007/s12265-019-09882-5. Epub 2019 Mar 18.
RGD ID: 151665136
Pubmed: PMID:30887465   (View Abstract at PubMed)
DOI: DOI:10.1007/s12265-019-09882-5   (Journal Full-text)

Molecular events involved in acute myocardial infarction (AMI) still remain unclear. A rat AMI model and cardiomyocytes cultured in vitro were used to mimic hypoxic conditions, and the profiles of histone methylation-related gene expression were explored. The demethylase Kdm6a expression was significantly upregulated in the rat AMI model and in hypoxia induction. The apoptosis rate of cardiomyocytes was significantly exacerbated when Kdm6a was knocked down. The expression of the Na+/Ca2+ exchanger (Ncx) was significantly upregulated in cardiomyocytes under hypoxia. Knockdown of Kdm6a downregulated the Ncx expression via enhancing H3K27me3 modification on Ncx gene promoter, and attenuated the intracellular calcium influx ability in cardiomyocytes as a consequence. Kdm6a regulates Ncx expression through reducing the H3K27me3 level on the Ncx promoter or enhancer. This finding provides a basis for further study of Kdm6a as a new regulator for AMI development.

RGD Manual Disease Annotations    Click to see Annotation Detail View

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
KDM6AHumanmyocardial infarction  ISOKdm6a (Rattus norvegicus)mRNA:increased expression:myocardium (rat)RGD 
Kdm6aMousemyocardial infarction  ISOKdm6a (Rattus norvegicus)mRNA:increased expression:myocardium (rat)RGD 
Kdm6aRatmyocardial infarction  IEP mRNA:increased expression:myocardium (rat)RGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Kdm6aRatcellular response to hypoxia  IEP  RGD 
Kdm6aRatnegative regulation of hypoxia-induced intrinsic apoptotic signaling pathway  IMP  RGD 
Kdm6aRatpositive regulation of transcription by RNA polymerase II  IMP  RGD 
Kdm6aRatprotein modification process  IMP histone H3-K27 demethylationRGD 

Objects Annotated

Genes (Rattus norvegicus)
Kdm6a  (lysine demethylase 6A)

Genes (Mus musculus)
Kdm6a  (lysine (K)-specific demethylase 6A)

Genes (Homo sapiens)
KDM6A  (lysine demethylase 6A)

Additional Information