Li Yongnan, Wu Shuodong
The Sixth General Surgery Biliary & Vascular surgery Shengjing Hospital of China Medical University Shenyang City China.
Food Sci Nutr. 2020 Nov 8;9(1):209-216. doi: 10.1002/fsn3.1985. eCollection 2021 Jan.
Many studies have demonstrated that curcumin can downregulate mRNA levels of sterol regulatory element-binding proteins (SREBP-2); however, our study did not find similar results. This study was designed to demonstrate that curcumin inhibits the proteolytic process of SREBP-2 by first inhibiting the expression of membrane-bound transcription factor site-1 protease (S1P) rather than directly inhibiting SREBP-2 expression. After curcumin treatment, Caco-2 cells were collected to observe the dose- and time-dependent dynamics of precursor and mature SREBP-2, transcription factor-specific protein 1 (SP-1), and SREBP cleavage-activating protein (SCAP). After curcumin treatment, SREBP-2 distribution was detected in the cells and S1P protein expression was examined. Curcumin could downregulate mRNA levels of SREBP2, SP-1 and SCAP, but it did not simultaneously downregulate the expression of precursor SREBP-2 (pSREBP-2) and SCAP. Curcumin can inhibit the proteolytic process of SREBP-2, reduce the production of mature SREBP-2 (mSREBP-2), and change the cellular distribution of SREBP-2. The inhibitory effect of curcumin on SP-1 protein expression is short-acting. Curcumin could downregulate the mRNA and protein expression of S1P, but has no obvious inhibitory effect on the mRNA and protein expression of S2P (site-2 protease). Curcumin can inhibit the SREBP-2 proteolytic process to reduce mSREBP-2 which functions as a transcription factor, affecting the regulation of cholesterol metabolism-related genes. Curcumin does not directly inhibit the expression of mSREBP-2 protein, and it has no such inhibitory effect for at least a short period of time, although curcumin does reduce the amount of mSREBP-2 protein. S1P is a key protease in the hydrolysis of pSREBP-2 into mSREBP-2. Therefore, curcumin may decrease the amount of mSREBP-2 by directly inhibiting the expression of S1P mRNA and protein.
许多研究表明，姜黄素可下调固醇调节元件结合蛋白（SREBP-2）的mRNA水平；然而，我们的研究并未发现类似结果。本研究旨在证明，姜黄素通过首先抑制膜结合转录因子位点-1蛋白酶（S1P）的表达，而非直接抑制SREBP-2的表达，来抑制SREBP-2的蛋白水解过程。姜黄素处理后，收集Caco-2细胞，观察前体和成熟SREBP-2、转录因子特异性蛋白1（SP-1）和SREBP裂解激活蛋白（SCAP）的剂量和时间依赖性动态变化。姜黄素处理后，检测细胞中SREBP-2的分布，并检测S1P蛋白表达。姜黄素可下调SREBP2、SP-1和SCAP的mRNA水平，但并未同时下调前体SREBP-2（pSREBP-2）和SCAP的表达。姜黄素可抑制SREBP-2的蛋白水解过程，减少成熟SREBP-2（mSREBP-2）的产生，并改变SREBP-2的细胞分布。姜黄素对SP-1蛋白表达的抑制作用是短效的。姜黄素可下调S1P的mRNA和蛋白表达，但对S2P（位点-2蛋白酶）的mRNA和蛋白表达无明显抑制作用。姜黄素可抑制SREBP-2的蛋白水解过程，以减少作为转录因子的mSREBP-2，影响胆固醇代谢相关基因的调控。姜黄素并不直接抑制mSREBP-2蛋白的表达，至少在短时间内没有这种抑制作用，尽管姜黄素确实减少了mSREBP-2蛋白的量。S1P是将pSREBP-2水解为mSREBP-2的关键蛋白酶。因此，姜黄素可能通过直接抑制S1P mRNA和蛋白的表达来减少mSREBP-2的量。
