Integrin-Dependent Akt1 Activation Regulates PGC-1 Expression and Fatty Acid Oxidation
Integrin-Dependent Akt1 Activation Regulates PGC-1 Expression and Fatty Acid Oxidation
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DOI：
10.1159/000332326
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发表时间：
2012-01-01
影响因子：
1.7
通讯作者：
Muise-Helmericks, Robin C.
中科院分区：
文献类型：
--
作者：
Beeson, Craig C.;Beeson, Gyda C.;Muise-Helmericks, Robin C.
背景：从海洋硅藻中提取的聚n -乙酰氨基葡萄糖纳米纤维已被用于促进皮肤伤口愈合。这些纳米纤维通过特异性激活整合素来发挥其活性，这使得它们成为解剖整合素介导途径的有用工具。我们已经证明，短纤维聚n -乙酰氨基葡萄糖纳米纤维（sNAG）处理内皮细胞可以在不增加细胞增殖的情况下增加细胞运动性和代谢率。结果：使用海马生物分析仪实时测量耗氧量，我们发现sNAG处理增加了耗氧量，这与整合素依赖性的Akt1激活相关。Akt1激活导致转录辅激活因子，过氧化物酶体增殖物激活受体γ辅激活因子-1 α (PGC-1 α)的表达增加。这不是由于线粒体生物发生的增加，而是与丙酮酸脱氢酶激酶4 （PDK4）表达的增加有关，表明脂肪酸氧化的调节。用依托莫西（一种o -肉碱棕榈酰基转移酶-1抑制剂）阻断脂肪酸氧化，可阻断snag依赖性的氧消耗增加。h -3棕榈酸盐摄取实验表明pdk4依赖性脂肪酸氧化增加，这是纳米纤维诱导的细胞运动所必需的。结论：我们的发现暗示了一条线性途径，即整合素依赖性的Akt1激活导致PGC-1 α和PDK4表达增加，从而通过脂肪酸氧化增加能量产生。巴塞尔S. Karger股份有限公司版权所有
Background: Poly-N-acetyl glucosamine nanofibers derived from a marine diatom have been used to increase cutaneous wound healing. These nanofibers exert their activity by specifically activating integrins, which makes them a useful tool for dissecting integrin-mediated pathways. We have shown that short-fiber poly-N-acetyl glucosamine nanofiber (sNAG) treatment of endothelial cells results in increased cell motility and metabolic rate in the absence of increased cell proliferation. Results: Using a Seahorse Bioanalyzer to measure oxygen consumption in real time, we show that sNAG treatment increases oxygen consumption rates, correlated with an integrin-dependent activation of Akt1. Akt1 activation leads to an increase in the expression of the transcriptional coactivator, peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1 alpha). This is not due to increased mitochondrial biogenesis, but is associated with an increase in the expression of pyruvate dehydrogenase kinase 4 (PDK4), suggesting regulation of fatty acid oxidation. Blockade of fatty acid oxidation with etomoxir, an O-carnitine palmitoyltransferase-1 inhibitor, blocks the sNAG-dependent increased oxygen consumption. H-3-palmitate uptake experiments indicate a PDK4-dependent increase in fatty acid oxidation, which is required for nanofiber-induced cell motility. Conclusions: Our findings imply a linear pathway whereby an integrin-dependent activation of Akt1 leads to increased PGC-1 alpha and PDK4 expression resulting in increased energy production by fatty acid oxidation. Copyright (C) 2012 S. Karger AG, Basel