通过不对称的阿尔金因甲基化来调节肝脏脂质生成
Hye-Sook Han1, Byeong Hun Choi1, Seo Young Jang2
1Division of Life Sciences, Korea University, Seoul 02841, Republic of Korea.
Metabolism: clinical and experimental
|May 25, 2024
概括
蛋白质氨酸甲基转移酶6 (PRMT6) 通过甲基化LXRα促进肝脏脂质生成,增强脂质积累. 抑制PRMT6会降低肝脏脂肪,这表明PRMT6是代谢疾病治疗的目标.
科学领域:
- 代谢调节 代谢调节 代谢调节
- 分子生物学分子生物学
- 肝病学 肝病学是一种肝病学.
背景情况:
- 肝脂肪生成将多余的碳水化合物转化为三糖醇 (TAG),导致非酒精性脂肪肝疾病 (NAFLD).
- 蛋白质氨酸甲基转移酶6 (PRMT6) 影响各种代谢过程,但其在肝脏脂肪生成中的作用尚不清楚.
研究的目的:
- 阐明PRMT6在调节肝脂生成和脂质代谢中的作用.
- 研究PRMT6控制脂质生成的分子机制.
主要方法:
- 同免疫沉以评估PRMT6-LXRα相互作用.
- 在LCRalpha.上识别甲基化氨酸残留物的LC-MS/MS.
- 路西法酶测试以评估SREBP-1c促进体活性.
- 在体外研究中,使用肝细胞进行PRMT6操纵 (宫外表达/shRNA).
- 在体内对小鼠进行的研究,小鼠在肝脏中操纵了LXRα或PRMT6.
主要成果:
- PRMT6激活了固醇调节元素结合蛋白 (SREBP) 1c促进活性.
- PRMT6与LXRα结合并甲基化它,增强LXRα活性.
- 过度表达PRMT6会增加脂原基因表达和肝细胞中的脂质积累.
- 抑制PRMT6可以降低脂原基因表达和脂质积累.
- 通过PRMT6介导的LXRα甲基化促进了小异构体合作伙伴 (SHP) 的解离,这是一种联合抑制剂.
- 在体内,受损的LXRα甲基化减少了小鼠的肝脂积累.
结论:
- PRMT6通过在阿金宁253的不对称二甲基化来调节LXRα活性,阻断SHP抑制.
- 通过调节LXRα介导的脂质生成,PRMT6对于控制肝脂质平衡至关重要.
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