LLRLTDL 和 GYALPCDCL 两种肽通过激活经 oxLDL 处理的 RAW264.7 巨噬细胞中的 PPAR-γ/LXR-α 信号通路,抑制泡沫细胞的形成。

IF 5 3区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
BioFactors Pub Date : 2024-05-17 DOI:10.1002/biof.2075
Chathuri Kaushalya Marasinghe, Soon-Do Yoon, Jae-Young Je
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引用次数: 0

摘要

泡沫细胞的形成在动脉粥样硬化相关心血管疾病中起着关键作用。从海洋中提取的生物活性肽具有多功能的健康优势。在本研究中,我们通过评估 LLRLTDL(Bu1)和 GYALPCDCL(Bu2)肽对氧化低密度脂蛋白(oxLDL)诱导的泡沫细胞形成的抑制作用,研究了从蚶壳蛋白水解物中分离的这两种肽的抗动脉粥样硬化作用。这两种肽通过抑制泡沫细胞的形成而显示出良好的抗动脉粥样硬化作用,这一点通过抑制氧化低密度脂蛋白(oxLDL)处理的 RAW264.7 巨噬细胞和氧化低密度脂蛋白处理的原代人主动脉平滑肌细胞(HASMC)中的脂质积累得到了证明。两种肽通过上调胆固醇外流和下调胆固醇流入,有效降低了总胆固醇、游离胆固醇、胆固醇酯和甘油三酯的水平。胆固醇流入相关蛋白(如 SR-A1 和 CD36)的表达减少,而胆固醇流出相关蛋白(如 ATP 结合盒转运体 ABCA-1 和 ABCG-1)则高表达。此外,Bu1 和 Bu2 肽增加了 PPAR-γ 和 LXR-α 的表达。然而,转染 PPAR-γ siRNA 逆转了 Bu1 和 Bu2 肽抑制泡沫细胞形成的活性。此外,在 PPAR-γ 激动剂噻唑烷二酮类药物的作用下,Bu1 和 Bu2 肽对泡沫细胞形成的抑制具有协同作用,这表明 PPAR-γ 信号通路在巨噬细胞泡沫细胞形成过程中起着关键作用。除了对泡沫细胞形成的影响外,Bu1 和 Bu2 肽还通过抑制促炎细胞因子和一氧化氮的生成以及 NF-κB 核活化而显示出抗炎潜力。综上所述,这些结果表明,Bu1 和 Bu2 肽可用于动脉粥样硬化和相关的抗炎疗法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Two peptides LLRLTDL and GYALPCDCL inhibit foam cell formation through activating PPAR-γ/LXR-α signaling pathway in oxLDL-treated RAW264.7 macrophages.

Two peptides LLRLTDL and GYALPCDCL inhibit foam cell formation through activating PPAR-γ/LXR-α signaling pathway in oxLDL-treated RAW264.7 macrophages.

Foam cell formation plays a pivotal role in atherosclerosis-associated cardiovascular diseases. Bioactive peptides generated from marine sources have been found to provide multifunctional health advantages. In the present study, we investigated the anti-atherosclerotic effects of LLRLTDL (Bu1) and GYALPCDCL (Bu2) peptides, isolated from ark shell protein hydrolysates by assessing their inhibitory effect on oxidized LDL (oxLDL)-induced foam cell formation. The two peptides showed a promising anti-atherosclerotic effect by inhibiting foam cell formation, which was evidenced by inhibiting lipid accumulation in oxLDL-treated RAW264.7 macrophages and oxLDL-treated primary human aortic smooth muscle cells (HASMC). Two peptides effectively reduced total cholesterol, free cholesterol, cholesterol ester, and triglyceride levels by upregulating cholesterol efflux and downregulating cholesterol influx. Expression of cholesterol influx-related proteins such as SR-A1 and CD36 were reduced, whereas cholesterol efflux-related proteins such as ATP-binding cassette transporter ABCA-1 and ABCG-1 were highly expressed. In addition, Bu1 and Bu2 peptides increased PPAR-γ and LXR-α expression. However, PPAR-γ siRNA transfection reversed the foam cell formation inhibitory activity of Bu1 and Bu2 peptides. Furthermore, the synergistic effect of Bu1 and Bu2 peptides on foam cell formation inhibition was observed with PPAR-γ agonist thiazolidinediones, indicating that PPAR-γ signaling pathway plays a key role in foam cell formation of macrophages. Beyond their impact on foam cell formation, Bu1 and Bu2 peptides demonstrated anti-inflammatory potential by inhibiting the generation of pro-inflammatory cytokines and nitric oxide and NF-κB nuclear activation. Taken together, these results suggest that Bu1 and Bu2 peptides may be useful for atherosclerosis and associated anti-inflammatory therapies.

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来源期刊
BioFactors
BioFactors 生物-内分泌学与代谢
CiteScore
11.50
自引率
3.30%
发文量
96
审稿时长
6-12 weeks
期刊介绍: BioFactors, a journal of the International Union of Biochemistry and Molecular Biology, is devoted to the rapid publication of highly significant original research articles and reviews in experimental biology in health and disease. The word “biofactors” refers to the many compounds that regulate biological functions. Biological factors comprise many molecules produced or modified by living organisms, and present in many essential systems like the blood, the nervous or immunological systems. A non-exhaustive list of biological factors includes neurotransmitters, cytokines, chemokines, hormones, coagulation factors, transcription factors, signaling molecules, receptor ligands and many more. In the group of biofactors we can accommodate several classical molecules not synthetized in the body such as vitamins, micronutrients or essential trace elements. In keeping with this unified view of biochemistry, BioFactors publishes research dealing with the identification of new substances and the elucidation of their functions at the biophysical, biochemical, cellular and human level as well as studies revealing novel functions of already known biofactors. The journal encourages the submission of studies that use biochemistry, biophysics, cell and molecular biology and/or cell signaling approaches.
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