Differential effects of and mechanisms underlying the protection of cardiomyocytes by liver-X-receptor subtypes against high glucose stress-induced injury

Liver-X-receptors (LXRs) are ligand-activated transcription factors belonging to the nuclear receptor superfamily. The two popular homologous receptor subtypes, LXRα and LXRβ, exhibit differential expression patterns, thereby probably playing different roles in different contexts. This study aimed to evaluate the different roles of the two LXR subtypes and the mechanisms underlying their protection of cardiomyocytes against high-glucose stress. Silencing of LXRα, but not LXRβ impaired normal LXR-mediated cardioprotective effects against high glucose-induced oxidative stress, apoptosis, and inflammation. Mechanistically, silencing of small ubiquitin-like modifier (SUMO)1 or SUMO2/3 did not affect LXR-mediated cardioprotective effects; however, these were impaired in response to nuclear receptor corepressor (NCoR) silencing. Together, these findings indicate that LXRα, but not LXRβ, protects against high glucose-induced cardiomyocyte injury, probably via the NCoR-dependent transrepression of downstream target genes.