Institute of Cardiovascular and Metabolic Research. The Schools of Biological Sciences and Pharmacy, University of Reading, Reading Berkshire, United Kingdom.
FEBS Open Bio. 2012 Jun 4;2:135-44. doi: 10.1016/j.fob.2012.05.005. Print 2012.
Adaptor proteins play an important role in signaling pathways by providing a platform on which many other proteins can interact. Malfunction or mislocalization of these proteins may play a role in the development of disease. Lipoma preferred partner (LPP) is a nucleocytoplasmic shuttling adaptor protein. Previous work shows that LPP plays a role in the function of smooth muscle cells and in atherosclerosis. In this study we wanted to determine whether LPP has a role in the myocardium. LPP expression increased by 56% in hearts from pressure overload aortic-banded rats (p < 0.05 n = 4), but not after myocardial infarction, suggesting hemodynamic load regulates its expression. In vitro, LPP expression was 87% higher in cardiac fibroblasts than myocytes (p < 0.05 n = 3). LPP expression was downregulated in the absence of the actin cytoskeleton but not when microtubules were disassembled. We mechanically stretched cardiac fibroblasts using the Flexcell 4000 for 48 h (1 Hz, 5% maximum strain), which decreased total LPP total expression and membrane localization in subcellular fractions (p < 0.05, n = 5). However, L-NAME, an inhibitor of nitric oxide synthase (NOS), significantly upregulated LPP expression. These findings suggest that LPP is regulated by a complex interplay between NO and mechanical cues and may play a role in heart failure induced by increased hemodynamic load.
衔接蛋白通过提供许多其他蛋白质可以相互作用的平台，在信号通路中发挥重要作用。这些蛋白质的功能障碍或定位错误可能在疾病的发展中起作用。脂肪优先伙伴（LPP）是一种核质穿梭衔接蛋白。以前的工作表明，LPP 在平滑肌细胞功能和动脉粥样硬化中起作用。在这项研究中，我们想确定 LPP 是否在心肌中起作用。压力超负荷主动脉带大鼠心脏中的 LPP 表达增加了 56%（p<0.05，n=4），但心肌梗死后没有增加，这表明血流动力学负荷调节其表达。在体外，心肌成纤维细胞中的 LPP 表达比心肌细胞高 87%（p<0.05，n=3）。在没有肌动蛋白细胞骨架的情况下，LPP 表达下调，但微管解聚时不表达。我们使用 Flexcell 4000 机械拉伸心肌成纤维细胞 48 小时（1Hz，最大应变 5%），这导致总 LPP 总表达和亚细胞分数中膜定位减少（p<0.05，n=5）。然而，一氧化氮合酶（NOS）抑制剂 L-NAME 显著上调 LPP 表达。这些发现表明，LPP 受 NO 和机械线索之间的复杂相互作用调节，可能在血流动力学负荷增加引起的心力衰竭中起作用。
