D-4F decreases the expression of Aβ protein through up-regulating long non coding RNA sirt1-as in SAMP8 mice

Abstract

Background and objective: 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. Keywords: D-4F, Sirt1-as, SAMP8, Aβ protein, Long non coding RNA