Elevated expression of liver X receptor alpha (LXRα) in myocardium of streptozotocin-induced diabetic rats.
The present study was designed to investigate the myocardial expression of liver X receptor alpha (LXRα) in a streptozotocin (STZ)-induced diabetic rat model. Immunohistochemical staining, quantitative real-time RT-PCR, and Western blot analysis were used to determine the expression of LXRα in the myocardium of STZ-induced diabetic rats. The myocardial expression of LXRα target genes, long-chain acyl-CoA synthetase 3 (ACSL3), fatty acid transporter protein (FAT/CD36), ATP-binding cassette transporter A1 (ABCA1), and ABCG1 were also detected. Bisulfite sequencing analysis was employed to examine the methylation status of the CpG island at the LXRα promoter region in the myocardium of STZ-induced diabetic rats. We found that LXRα mRNA and protein expression in the left ventricles, right ventricles, and atria of diabetic rats were gradually increased during the progression of diabetic cardiomyopathy (DCM). The mRNA expression levels of ACSL3 and FAT/CD36 and the protein expression levels of ABCA1 and ABCG1 were also markedly increased in different heart chambers of diabetic rats. Moreover, there was a significant difference in the methylation status of LXRα gene between the ventricles of control and diabetic rats (P < 0.05). Our findings suggest that elevated expression of LXRα may be involved in the progression of DCM, and demethylation of LXRα is likely to be responsible for its increased expression in myocardial tissues.
Department of Pathology, Shengjing Hospital Affiliated to China Medical University, 36 Sanhao Street, Shenyang, 110004, People's Republic of China.
Yongxia
Y
Cheng
Guibo
G
Liu
Qian
Q
Pan
Sufen
S
Guo
Xianghong
X
Yang
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000473:pathology*; D018450:Disease Progression; D006352:Heart Ventricles / Q000378:metabolism; D000071518:Liver X Receptors; D008745:Methylation; D009206:Myocardium / Q000378:metabolism*; D057093:Orphan Nuclear Receptors / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D015854:Up-Regulation / Q000235:genetics*
D000071518:Liver X Receptors; C000605215:Nr1h3 protein, rat; D057093:Orphan Nuclear Receptors; D012333:RNA, Messenger