Differential effects of and mechanisms underlying the protection of cardiomyocytes by liver-X-receptor subtypes against high glucose stress-induced injury
Differential effects of and mechanisms underlying the protection of cardiomyocytes by liver-X-receptor subtypes against high glucose stress-induced injury
复制标题
肝X受体亚型保护心肌细胞对抗高糖应激损伤的不同作用和机制
DOI：
10.1016/j.bbrc.2018.07.050
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发表时间：
2018
影响因子：
3.1
通讯作者：
Zhang Junfeng
中科院分区：
文献类型：
--
作者：
He Qing;Wang Fengdan;Fan Yuqi;Wang Changqian;Zhang Junfeng
肝脏X受体（LXRs）是核受体超家族中的配体激活的转录因子。两种流行的同源受体亚型LXRα和LXRβ表现出不同的表达模式，因此可能在不同的背景下发挥不同的作用。本研究旨在评价两种LXR亚型的不同作用及其保护心肌细胞免受高糖应激的机制。沉默LXR α而非LXR β可损害正常LXR介导的心脏保护作用，对抗高糖诱导的氧化应激、细胞凋亡和炎症。从机制上讲，小泛素样修饰物（SUMO）1或SUMO 2/3的沉默并不影响LXR介导的心脏保护作用;然而，这些作用在响应核受体辅阻遏物（NCoR）沉默中受损。总之，这些研究结果表明，LXRα，而不是LXRβ，保护免受高糖诱导的心肌细胞损伤，可能通过下游靶基因的NCoR依赖性反式阻遏。
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 ofLXRα, but notLXRβimpaired normal LXR-mediated cardioprotective effects against high glucose-induced oxidative stress, apoptosis, and inflammation. Mechanistically, silencing ofsmall ubiquitin-like modifier (SUMO)1orSUMO2/3did not affect LXR-mediated cardioprotective effects; however, these were impaired in response tonuclear 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.