n-3 PUFA as Regulators of Cardiac Gene Transcription: A New Link between PPAR Activation and Fatty Acid Composition
n-3 PUFA as Regulators of Cardiac Gene Transcription: A New Link between PPAR Activation and Fatty Acid Composition
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DOI：
10.1007/s11745-009-3362-y
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发表时间：
2009-12-01
期刊：
影响因子：
1.9
通讯作者：
Bordoni, Alessandra
中科院分区：
文献类型：
--
作者：
Di Nunzio, Mattia;Danesi, Francesca;Bordoni, Alessandra
脂肪酸调节基因表达，直接结合到核受体或影响转录因子的蛋白质含量。在这项工作中，用60 μ M EPA或DHA补充新生大鼠心肌细胞的原代培养物，我们通过ELISA测定证明了增加的PPAR β/δ与DNA的结合。n-3 PUFA的补充深刻地改变了细胞质和核馏分的酰基组成。总脂肪酸的高含量，特别是EPA和DHA，以及补充后的增加表明n-3 PUFA在细胞核中的选择性积累，支持n-3 PUFA与PPAR的直接相互作用。在补充n-3 PUFA的细胞中，酰基辅酶A硫酯酶（ACOT）催化从酰基辅酶A产生NEFA的反应的活性增加。NEFA/酰基辅酶A比率是脂肪酸转运到细胞核和随后调节基因转录的重要调节因子，尽管ACOT活性不是该比率的唯一参数，但它对于NEFA池组成的控制很重要。我们的数据进一步阐明了补充n-3 PUFA后心肌细胞中发生的情况，将酰基组成的修饰与ACOT活性和PPAR活化联系起来。
The fatty acids regulate gene expression directly binding to nuclear receptors or affecting the protein content of transcription factors. In this work, supplementing primary cultures of neonatal rat cardiomyocytes with 60 A mu M EPA or DHA, we demonstrated by an ELISA assay an increased PPAR beta/delta binding to DNA. n-3 PUFA supplementation deeply changed the acyl composition of both cytosolic and nuclear fractions. The high content of total fatty acids, particularly EPA and DHA, and its increase following supplementation suggested a selective accumulation of n-3 PUFAs in the nucleus, supporting the direct interaction of n-3 PUFA with PPAR. The activity of acyl-CoA thioesterase (ACOT), catalyzing the reaction leading to NEFA from acyl-CoA, increased in n-3 PUFA supplemented cells. The NEFA/acyl-CoA ratio is an important regulator of the fatty acid transport to the nucleus and consequent modulation of gene transcription, and although ACOT activity is not the only parameter of this ratio, it is important for the control of the NEFA pool composition. Our data further clarify what happens in cardiomyocytes following n-3 PUFA supplementation, linking the modification of acyl composition to ACOT activity and PPAR activation.