Protein markers of dysfunctional HDL in scavenger receptor class B type I deficient mice.
Protein markers of dysfunctional HDL in scavenger receptor class B type I deficient mice.
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B 类清道夫受体 I 型缺陷小鼠功能障碍 HDL 的蛋白质标记
DOI：
10.1186/s12967-018-1502-y
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发表时间：
2018-06-07
影响因子：
7.4
通讯作者：
Yu H
中科院分区：
文献类型：
--
作者：
Cao J;Xu Y;Li F;Shang L;Fan D;Yu H
背景清道夫受体B类I型（SR-BI）在高密度脂蛋白（HDL）代谢中起关键作用。SR-BI缺乏导致小鼠对动脉粥样硬化的易感性增加，伴有异常大、胆固醇富集和功能受损的HDL。本研究旨在表征SR-BI缺陷小鼠（SR-BI−/−）中功能失调的HDL蛋白标记物，并检测普罗布考治疗是否会影响HDL的缺陷。方法采用鸟枪蛋白质组学和二维凝胶电泳技术对SR-BI−/−小鼠的HDL蛋白谱和HDL颗粒分布进行分析。测定HDL的细胞功能、对氧磷酶1 （PON1）和髓过氧化物酶活性。1.2 mg/g/d普罗布考连续治疗6周，分析其对HDL蛋白标志物的影响。Western blotting对差异蛋白进行定量。结果与野生型（WT）小鼠相比，SR-BI−/−HDL蛋白的相对含量降低了约25%。与WT HDL相比，SR-BI−/−HDL中代表性apoAI和PON1的相对蛋白丰度显著降低，而急性期蛋白血清淀粉样蛋白A （SAA）和apoAIV、蛋白酶抑制剂α-1-抗胰蛋白酶（A1AT）的相对蛋白丰度升高。SR-BI - / -小鼠血浆中含apoAI的HDL颗粒的分布也发生了显著变化，尽管血浆apoAI水平没有差异。蛋白质的改变伴随着SR-BI−/−HDL的功能障碍，巨噬细胞中胆固醇稳态受损，抗氧化和抗炎作用降低。Probucol治疗SR-BI - / -小鼠可恢复apoAI、PON1、SAA、apoAIV和A1AT等关键蛋白对HDL的相对含量，在降低HDL- c水平的同时改善HDL功能障碍。结论sr - bi缺乏导致HDL功能障碍与HDL蛋白改变密切相关，提示apoAI、PON1、SAA、apoAIV和A1AT的鉴定可作为诊断和治疗功能障碍HDL相关代谢性疾病的有价值的蛋白标志物。
BackgroundScavenger receptor class B type I (SR-BI) plays a key role in high density lipoproteins (HDL) metabolism. SR-BI deficiency in mice results in enhanced susceptibility to atherosclerosis with abnormal large, cholesterol enriched, and functional impaired HDL. This study was to characterize the protein markers of dysfunctional HDL in SR-BI deficient (SR-BI−/−) mice and to test if the defective of HDL might be affected by probucol treatment.MethodsShotgun proteomics and 2-D gel electrophoresis were performed to examine the profile of HDL protein and distribution of HDL particles isolated from SR-BI−/−mice. HDL’s cell-function, paraoxonase 1 (PON1) and myeloperoxidase activity were assessed. The mice were treated with 1.2 mg/g/day probucol for 6 weeks and the impact on HDL protein markers was analyzed. The differential proteins were quantified by Western blotting.ResultsThe relative amount of protein in SR-BI−/−HDL was decreased by about 25% compared to that in HDL from wild type (WT) mice. Compared to WT HDL, relative protein abundance of representative apoAI and PON1 in SR-BI−/−HDL were significantly reduced, whereas acute-phase protein serum amyloid A (SAA) and apoAIV, proteinase inhibitor proteins α-1-antitrypsin (A1AT) were increased. The distribution of plasma apoAI-containing HDL particles in SR-BI−/−mice was also dramatically altered, although plasma apoAI level was no difference. The protein alterations were accompanied with dysfunction of SR-BI−/−HDL, evidenced by impaired cholesterol homeostasis in macrophages, and reduced anti-oxidative and anti-inflammatory effects. Probucol treatment of SR-BI−/−mice could restored the relative contents of critical proteins including apoAI, PON1, SAA, apoAIV and A1AT on HDL, and improve HDL dysfunction despite decreased HDL-C level.ConclusionSR-BI deficiency leading to dysfunctional HDL is closely related to alteration of HDL protein, suggesting that identification of apoAI, PON1, SAA, apoAIV, and A1AT may serve as the valuable protein markers for diagnosis and therapeutics of dysfunctional HDL-related metabolic diseases.
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影响因子：
5.3
作者：
Khovidhunkit, W;Duchateau, PN;Feingold, KR
通讯作者：
Feingold, KR
影响因子：
37.8
作者：
Rosenson RS;Brewer HB Jr;Davidson WS;Fayad ZA;Fuster V;Goldstein J;Hellerstein M;Jiang XC;Phillips MC;Rader DJ;Remaley AT;Rothblat GH;Tall AR;Yvan-Charvet L
通讯作者：
Yvan-Charvet L
清道夫受体 BI 和高密度脂蛋白调节脓毒症中胸腺细胞凋亡。
DOI：
10.1161/atvbaha.113.302484
发表时间：
2014-05
期刊：
Arteriosclerosis, thrombosis, and vascular biology
影响因子：
--
作者：
Guo L;Zheng Z;Ai J;Howatt DA;Mittelstadt PR;Thacker S;Daugherty A;Ashwell JD;Remaley AT;Li XA
通讯作者：
Li XA
影响因子：
15.9
作者：
Miettinen, HE;Rayburn, H;Krieger, M
通讯作者：
Krieger, M
影响因子：
13.6
作者：
Burger, Danielle;Dayer, Jean-Michel
通讯作者：
Dayer, Jean-Michel