D-4F decreases the expression of Aβ protein through up-regulating long non coding RNA sirt1-as in SAMP8 mice.
D-4F decreases the expression of Aβ protein through up-regulating long non coding RNA sirt1-as in SAMP8 mice.
复制标题
DOI：
10.1016/j.jsps.2017.04.017
复制
发表时间：
2017-05
期刊：
影响因子：
--
通讯作者：
Ye P
中科院分区：
文献类型：
--
作者：
Ding XH;Han J;Liu Y;Jin Y;Ye P
胆固醇在 (Aβ) 代谢和产生中起着关键作用。 D-4F 是载脂蛋白 A-I 模拟肽，已被证明在调节胆固醇方面具有关键作用。我们的目的是确定 D-4F 对 SAMP8 中 Aβ 产生的影响及其潜在机制。方法：SAMP8 小鼠 (n = 15) 被随机分为三组，接受饮用水中的 D-4F 治疗：高剂量组 (0.5 mg/ml)、低剂量组 (0.3 mg/ml) 和对照组（仅饮用水）。心脏、肾脏、肝脏和大脑取自 SAMP8（其中 9 个纳入分析）。在所有组织中均测量了长非编码 RNA Sirt1-as。进行免疫组织化学、蛋白质印迹qRT-PCR来测定sirt1-as和相关蛋白或RNA的水平。结果：用D-4F治疗后，sirt1-as在大脑中显着上调，而不是在心脏、肾脏或肝脏中。特别是，与对照组相比，海马区高剂量 D-4F 显着上调 Sirt1-as (p = 0.007)。进一步分析表明D-4F上调SIRT1的表达。我们还发现，D-4F 治疗显着增加了反向胆固醇转运相关蛋白肝脏 X 受体 α (LXRα) 和 ATP 结合盒转运蛋白 A1 (ABCA1，p < 0.05)。最后，β淀粉样蛋白（Aβ蛋白）在统计学上低于对照组（p < 0.05）。结论：我们的观察表明，D-4F 通过上调长链非编码 RNA Sirt1-as 及其下游蛋白来降低 Aβ 蛋白的表达，这些蛋白可能参与胆固醇反向转运。
Cholesterol plays key roles on (Aβ) metabolism and production. D-4F is the apolipoprotein A-I mimetic peptide which has been revealed a critical role in regulation cholesterol. We aimed at identifying the effects of D-4F on Aβ production in SAMP8 and the underlying mechanisms. Methods: SAMP8 mice (n = 15) were randomized into three groups for treatment with D-4F given in drinking water: high-dose group (0.5 mg/ml), low-dose group (0.3 mg/ml) and control group (just drinking water). The heart, kidney, liver and brain were obtained from SAMP8 (9 of them included in the analysis). The long non-coding RNA sirt1-as was measured in all tissues. The immunohistochemistry, western blot qRT-PCR were performed to determine the sirt1-as and the relevant proteins or RNAs levels. Results: After treated with D-4F, the sirt1-as has been significantly upregulated in brain, rather than heart, kidney or liver. Specially, sirt1-as was significantly up-regulated by high dose of D-4F in the hippocampus area (p = 0.007) compared with control group. Further analysis revealed that D-4F up-regulates the expression of SIRT1. We also found that D-4F treatment significantly increased the reverse cholesterol transport related proteins liver X receptor α (LXRα) and ATP-binding cassette transporter A1 (ABCA1, p < 0.05). Finally, the amyloid β-protein (Aβ protein) was statistically lower than that in the control group (p < 0.05). Conclusion: Our observation indicated that D-4F decreases the expression of Aβ protein through up-regulating long non coding RNA sirt1-as and its downstream proteins which may involve in reverse cholesterol transport.