Chrysin reduces the activity and protein level of mature forms of sterol regulatory element-binding proteins
Chrysin reduces the activity and protein level of mature forms of sterol regulatory element-binding proteins
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DOI：
10.1080/09168451.2019.1608806
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发表时间：
2019-11-02
影响因子：
1.6
通讯作者：
Sato, Ryuichiro
中科院分区：
文献类型：
--
作者：
Iwase, Masamori;Watanabe, Kyoko;Sato, Ryuichiro
固醇调节元件结合蛋白(SREBPs)是调节脂肪酸和胆固醇生物合成途径相关基因表达的转录因子。本研究表明，黄酮类白杨素对脂肪酸合成酶启动子有损伤作用。白杨素降低人肝癌Huh-7细胞中SREBP靶基因的表达，如脂肪酸合成酶，并损害脂肪酸和胆固醇的从头合成。此外，它还减少了SREBPs的内源成熟、转录活性形式，这些形式是由前体形式的蛋白分解处理产生的。此外，白杨素降低了SREBPs的强制表达成熟形式及其转录活性。泛素-蛋白酶体系统不参与白杨素介导的SREBPs成熟形式的减少。这些结果表明，白杨素至少部分地通过降解SREBPs成熟形式来抑制SREBP的活性。缩写：ACC1：乙酰-CoA羧基酶1；DMEM：Dulbecco‘s改良的Eagle’s培养基；Fas：脂肪酸合成酶；GAPDH：甘油醛-3-磷酸脱氢酶；25-HC：25-羟基胆固醇；HMGCS：HMG-CoA合成酶；LDH：乳酸脱氢酶；LPDS：脂蛋白缺乏的血清；PI3K：磷脂酰肌醇3-激酶；SCD1：硬脂酰辅酶A脱氢酶；SREBPS：醇调节元素结合蛋白。
Sterol regulatory element-binding proteins (SREBPs) are transcription factors that regulate the expression of genes involved in fatty acid and cholesterol biosynthetic pathways. The present study showed that the flavonoid chrysin impairs the fatty acid synthase promoter. Chrysin reduces the expression of SREBP target genes, such as fatty acid synthase, in human hepatoma Huh-7 cells and impairs de novo synthesis of fatty acids and cholesterol. Moreover, it reduces the endogenous mature, transcriptionally active forms of SREBPs, which are generated by the proteolytic processing of precursor forms. In addition, chrysin reduces the enforced expressing mature forms of SREBPs and their transcriptional activity. The ubiquitin-proteasome system is not involved in the chrysin-mediated reduction of SREBPs mature forms. These results suggest that chrysin suppresses SREBP activity, at least partially, via the degradation of SREBPs mature forms.Abbreviations: ACC1: acetyl-CoA carboxylase 1; DMEM: Dulbecco's modified Eagle's medium; FAS: fatty acid synthase; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; 25-HC: 25-hydroxycholesterol; HMGCS: HMG-CoA synthase; LDH: lactate dehydrogenase; LPDS: lipoprotein-deficient serum; PI3K: phosphatidylinositol 3-kinase; SCD1: stearoyl-CoA desaturase; SREBPs: sterol regulatory element-binding proteins.