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蓝绿藻球形念珠藻变种的脂质提取物可抑制HepG2细胞中固醇调节元件结合蛋白的激活。

Lipid extract of Nostoc commune var. sphaeroides Kutzing, a blue-green alga, inhibits the activation of sterol regulatory element binding proteins in HepG2 cells.

作者信息

Rasmussen Heather E, Blobaum Kara R, Park Young-Ki, Ehlers Sarah J, Lu Fan, Lee Ji-Young

机构信息

Department of Nutrition, University of Nebraska, Lincoln, NE 68583, USA.

出版信息

J Nutr. 2008 Mar;138(3):476-81. doi: 10.1093/jn/138.3.476.

Abstract

Nostoc commune var. sphaeroides Kützing (N. commune), a blue-green alga, has been used as both a food ingredient and in medicine for centuries. To determine the effect of N. commune on cholesterol metabolism, N. commune lipid extract was incubated at increasing concentrations (25-100 mg/L) with HepG2 cells, a human hepatoma cell line. The addition of N. commune lipid extract markedly reduced mRNA abundance of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) and LDL receptor (LDLR) (P < 0.05), with a concomitant decrease in their protein expression (P < 0.001). Reduced HMGR activity by 90% with N. commune lipid extract confirmed the inhibitory role of N. commune in cholesterol synthesis (P < 0.006). To elucidate a molecular mechanism underlying the repression of HMGR and LDLR by N. commune lipid extract, expression of sterol regulatory element binding protein 2 (SREBP-2) was assessed. Whereas mRNA for SREBP-2 remained unchanged, SREBP-2 mature protein was reduced by N. commune (P < 0.009). In addition, N. commune lipid extract also decreased SREBP-1 mature protein by approximately 30% (P < 0.002) and reduced the expression of SREBP-1-responsive genes such as fatty acid synthase and stearoyl CoA desaturase 1 (SCD-1) (P < 0.05). Therefore, our results demonstrate that N. commune lipid extract inhibits the maturation process of both SREBP-1 and -2, resulting in a decrease in expression of genes involved in cholesterol and fatty acid metabolism.

摘要

球状念珠藻变种(Nostoc commune var. sphaeroides Kützing,即普通念珠藻),一种蓝藻,数世纪以来一直被用作食品成分和药物。为了确定普通念珠藻对胆固醇代谢的影响,将普通念珠藻脂质提取物与人类肝癌细胞系HepG2细胞在浓度递增(25 - 100 mg/L)的条件下进行孵育。添加普通念珠藻脂质提取物显著降低了3-羟基-3-甲基戊二酰辅酶A还原酶(HMGR)和低密度脂蛋白受体(LDLR)的mRNA丰度(P < 0.05),同时其蛋白表达也随之降低(P < 0.001)。普通念珠藻脂质提取物使HMGR活性降低90%,证实了普通念珠藻在胆固醇合成中的抑制作用(P < 0.006)。为了阐明普通念珠藻脂质提取物抑制HMGR和LDLR的分子机制,评估了固醇调节元件结合蛋白2(SREBP-2)的表达。虽然SREBP-2的mRNA保持不变,但普通念珠藻使SREBP-2成熟蛋白减少(P < 0.009)。此外,普通念珠藻脂质提取物还使SREBP-1成熟蛋白减少约30%(P < 0.002),并降低了SREBP-1反应性基因如脂肪酸合酶和硬脂酰辅酶A去饱和酶1(SCD-1)的表达(P < 0.05)。因此,我们的结果表明,普通念珠藻脂质提取物抑制SREBP-1和-2的成熟过程,导致参与胆固醇和脂肪酸代谢的基因表达下降。

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