Comparative proteomics reveals abnormal binding of ATGL and dysferlin on lipid droplets from pressure overload-induced dysfunctional rat hearts.
Comparative proteomics reveals abnormal binding of ATGL and dysferlin on lipid droplets from pressure overload-induced dysfunctional rat hearts.
复制标题
比较蛋白质组学揭示 ATGL 和 Dysferlin 在压力超载引起的功能障碍大鼠心脏脂滴上的异常结合。
DOI：
10.1038/srep19782
复制
发表时间：
2016-01-22
影响因子：
4.6
通讯作者：
Liu P
中科院分区：
文献类型：
--
作者：
Li L;Zhang H;Wang W;Hong Y;Wang J;Zhang S;Xu S;Shu Q;Li J;Yang F;Zheng M;Qian Z;Liu P
中性脂质在心肌脂滴（LD）中的过度保留是心肌病的常见现象。因此，对心脏LD蛋白质组的系统研究将有助于剖析心脏脂肪变性和心肌功能障碍的潜在机制。在这里，在从正常和功能障碍的Sprague-Dawley大鼠心脏分离LD后，我们使用iTRAQ定量蛋白质组学方法鉴定了752种心脏相关LD蛋白，包括451种以前未报道的LD蛋白。最值得注意的发现是膜重新密封蛋白dysferlin的鉴定。对dysferlin截短突变体的分析表明，其C2结构域负责其LD定位。定量蛋白质组学结果进一步确定，与正常心脏相比，27种蛋白质在压力超负荷后诱导的功能障碍心脏的LD中增加，16种蛋白质减少。值得注意的是，脂肪三酰甘油脂肪酶（ATGL）显着降低，dysferlin显着增加功能障碍的心脏LD。该研究首次揭示了健康组织中心脏LD蛋白质组的数据集以及心功能不全时其变化。这些发现突出了改变的LD蛋白定位dysferlin和ATGL和心肌功能障碍之间的关联。
Excessive retention of neutral lipids in cardiac lipid droplets (LDs) is a common observation in cardiomyopathy. Thus, the systematic investigation of the cardiac LD proteome will help to dissect the underlying mechanisms linking cardiac steatosis and myocardial dysfunction. Here, after isolation of LDs from normal and dysfunctional Sprague-Dawley rat hearts, we identified 752 heart-associated LD proteins using iTRAQ quantitative proteomic method, including 451 proteins previously unreported on LDs. The most noteworthy finding was the identification of the membrane resealing protein, dysferlin. An analysis of dysferlin truncation mutants indicated that its C2 domain was responsible for its LD localization. Quantitative proteomic results further determined that 27 proteins were increased and 16 proteins were decreased in LDs from post pressure overload-induced dysfunctional hearts, compared with normal hearts. Notably, adipose triacylglycerol lipase (ATGL) was dramatically decreased and dysferlin was substantially increased on dysfunctional cardiac LDs. This study for the first time reveals the dataset of the heart LD proteome in healthy tissue and the variation of it under cardiac dysfunction. These findings highlight an association between the altered LD protein localization of dysferlin and ATGL and myocardial dysfunction.