Trafficking of endogenous smooth muscle cell cholesterol: a role for serum amyloid A and interleukin-1ýý.
Trafficking of endogenous smooth muscle cell cholesterol: a role for serum amyloid A and interleukin-1ýý.
复制标题
内源性平滑肌细胞胆固醇的贩运：血清淀粉样蛋白 A 和白细胞介素 1×× 的作用。
DOI：
10.1161/atvbaha.112.300243
复制
发表时间：
2012
期刊：
影响因子：
--
通讯作者：
Schreiber,BarbaraM
中科院分区：
文献类型：
--
作者：
PessolanoJr,LawrenceG;Sullivan,ChristopherP;Seidl,StephanieE;Rich,CelesteB;Liscum,Laura;Stone,PhillipJ;Sipe,JeanD;Schreiber,BarbaraM
细胞内胆固醇分布影响细胞功能;然而，影响内源性胆固醇运输的过程在很大程度上仍然未知。动脉粥样硬化与血管炎症和这些研究解决平滑肌细胞cholesterol trafficking.Methods和ResultsInterestingly的炎症介质的作用，在没有外源性胆固醇源，血清淀粉样蛋白A增加[14 C]油酸纳入大鼠平滑肌细胞胆固醇酯，这表明内源性胆固醇贩运到内质网。[3H]胆固醇酯在用[3 H]胆固醇预标记的细胞中积累，证实血清淀粉样蛋白A介导内源性胆固醇的运动。胆固醇运动依赖于功能性内溶酶体。在血清淀粉样蛋白A处理的细胞中，胆固醇的胆固醇氧化酶敏感池减少。此外，血清淀粉样蛋白A诱导胆固醇运输的机制被确定为通过激活分泌型磷脂酶A2，IIA组（sPLA 2）的表达和sPLA 2依赖性激活鞘磷脂酶。有趣的是，尽管肿瘤坏死因子-α和干扰素-γ均不诱导胆固醇运输，但白细胞介素-1 β诱导[14 C]胆固醇酯蓄积，这也依赖于sPLA 2和鞘磷脂酶活性。血清淀粉样蛋白A激活平滑肌细胞白细胞介素-1 β的表达，虽然白细胞介素-1受体拮抗剂抑制白细胞介素-1 β-诱导的胆固醇运输，它对血清淀粉样蛋白A介导的胆固醇运动没有影响。结论这些数据支持炎症在内源性平滑肌细胞胆固醇从质膜运输到内质网中的作用。
ObjectiveIntracellular cholesterol distribution impacts cell function; however, processes influencing endogenous cholesterol trafficking remain largely unknown. Atherosclerosis is associated with vascular inflammation and these studies address the role of inflammatory mediators on smooth muscle cell cholesterol trafficking.Methods and ResultsInterestingly, in the absence of an exogenous cholesterol source, serum amyloid A increased [14C] oleic acid incorporation into cholesteryl ester in rat smooth muscle cells, suggesting endogenous cholesterol trafficking to the endoplasmic reticulum. [3H] cholesteryl ester accumulated in cells prelabeled with [3H] cholesterol, confirming that serum amyloid A mediated the movement of endogenous cholesterol. Cholesterol movement was dependent upon functional endolysosomes. The cholesterol oxidase–sensitive pool of cholesterol decreased in serum amyloid A−treated cells. Furthermore, the mechanism whereby serum amyloid A induced cholesterol trafficking was determined to be via activation of expression of secretory phospholipase A2, group IIA (sPLA2) and sPLA2–dependent activation of sphingomyelinase. Interestingly, although neither tumor necrosis factor-α nor interferon-γ induced cholesterol trafficking, interleukin-1β induced [14C] cholesteryl ester accumulation that was also dependent upon sPLA2and sphingomyelinase activities. Serum amyloid A activates smooth muscle cell interleukin-1β expression, and although the interleukin-1–receptor antagonist inhibited the interleukin-1β−induced cholesterol trafficking, it had no effect on the movement of cholesterol mediated by serum amyloid A.ConclusionThese data support a role for inflammation in endogenous smooth muscle cell cholesterol trafficking from the plasma membrane to the endoplasmic reticulum.