Autophagy involved in lipopolysaccharide-induced foam cell formation is mediated by adipose differentiation-related protein.
Autophagy involved in lipopolysaccharide-induced foam cell formation is mediated by adipose differentiation-related protein.
复制标题
脂多糖诱导的泡沫细胞形成中涉及的自噬是由脂肪分化相关蛋白介导的。
DOI：
10.1186/1476-511x-13-10
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发表时间：
2014-01-09
影响因子：
4.5
通讯作者：
Ye J
中科院分区：
文献类型：
--
作者：
Feng X;Yuan Y;Wang C;Feng J;Yuan Z;Zhang X;Sui W;Hu P;Zheng P;Ye J
自噬是分解大分子和老化/受损的细胞器以维持细胞能量平衡和细胞营养状态的重要过程。自噬调节脂质代谢的观点是一个新兴概念，对动脉粥样硬化具有重要意义。然而，自噬在泡沫细胞形成中的潜在作用及其与脂质代谢的关系仍不清楚。在这项研究中，我们发现自噬参与了脂多糖（LPS）诱导的泡沫细胞的形成，并且至少部分依赖于脂肪分化相关蛋白（ADRP）。通过油红O染色评价泡沫细胞的形成。通过免疫荧光和蛋白质印迹测定自噬活性。通过实时PCR（RT-PCR）检查ADRP基因的表达。使用蛋白质印迹分析测量 ADRP 和 LC3 的蛋白表达。通过酶比色测定定量测量泡沫细胞中的细胞内胆固醇和甘油三酯水平。 LPS 通过诱导巨噬细胞中的脂质积累来促进泡沫细胞的形成。雷帕霉素（Rap）激活自噬降低了细胞内胆固醇和甘油三酯水平，而3-甲基腺嘌呤（3MA）抑制自噬则增强了脂滴的积累。 ADRP 单独过度表达会增加泡沫细胞的形成，从而增加自噬活性。相反，siRNA对ADRP活性的抑制作用抑制了自噬的激活。综上所述，我们提出 ADRP 在 LPS 刺激期间调节巨噬细胞自噬中的新作用。我们定义了一条新的分子途径，其中脂多糖诱导的泡沫细胞形成通过自噬进行调节。这些发现有助于理解自噬在动脉粥样硬化发展中的作用。
Autophagy is an essential process for breaking down macromolecules and aged/damaged cellular organelles to maintain cellular energy balance and cellular nutritional status. The idea that autophagy regulates lipid metabolism is an emerging concept with important implications for atherosclerosis. However, the potential role of autophagy and its relationship with lipid metabolism in foam cell formation remains unclear. In this study, we found that autophagy was involved in the lipopolysaccharide (LPS)-induced the formation of foam cells and was at least partially dependent on adipose differentiation-related protein (ADRP). Foam cell formation was evaluated by Oil red O staining. Autophagic activity was determined by immunofluorescence and Western blotting. ADRP gene expression of ADRP was examined by real-time PCR (RT-PCR). The protein expression of ADRP and LC3 was measured using Western blotting analysis. Intracellular cholesterol and triglyceride levels in foam cells were quantitatively measured by enzymatic colorimetric assays. LPS promoted foam cell formation by inducing lipid accumulation in macrophages. The activation of autophagy with rapamycin (Rap) decreased intracellular cholesterol and triglyceride levels, whereas the inhibition of autophagy with 3-methyladenine (3MA) enhanced the accumulation of lipid droplets. Overexpression of ADRP alone increased the formation of foam cells and consequently autophagic activity. In contrast, the inhibitory effects of ADRP activity with siRNA suppressed the activation of autophagy. Taken together, we propose a novel role for ADRP in the regulation of macrophage autophagy during LPS stimulation. We defined a new molecular pathway in which LPS-induced foam cell formation is regulated through autophagy. These findings facilitate the understanding of the role of autophagy in the development of atherosclerosis.