Effect of conjugated linoleic acid on inhibition of prolyl hydroxylase 1 in hearts of mice.
Effect of conjugated linoleic acid on inhibition of prolyl hydroxylase 1 in hearts of mice.
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DOI：
10.1186/1476-511x-11-22
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发表时间：
2012-02-07
影响因子：
4.5
通讯作者：
Li D
中科院分区：
文献类型：
--
作者：
Zhang J;Li D
不同的实验结果为cis-9，trans-11-conjugated linoleic acid（CLA）对心血管疾病的保护作用提供了证据。但CLA对脯氨酰羟化酶1（PHD 1）的抑制作用与其诱导缺氧诱导因子（HIF s）的产生有关，在此方面的研究尚未见报道。本研究的目的是评估两种主要的顺式-9，反式-11（c9，t11），反式-10，顺式-12（t10，c12）CLA异构体以及这两种异构体的混合物是否可以抑制PHD 1，诱导小鼠心肌中的HIF，以及随后对心肌代谢的影响。CLA混合物和c9，t11 CLA均抑制小鼠心肌PHD 1蛋白表达，增加HIF-2α蛋白和mRNA水平。同时，CLA混合物和c9，t11 CLA也能促进HIF相关转录因子PDK 4和PPARα的表达。c9，t11 CLA补充组小鼠心肌中基础代谢的重编程表现为GLUT 4基因表达的增加。CLA混合物和c9，t11 CLA均能增加UCP 2的表达，抑制ROS的产生。CLA混合物和c9，t11 CLA均能抑制PHD 1，诱导小鼠心肌组织中HIF-2α的表达，其机制可能与通过激活PPARα上调PDK 4有关。这一过程还意味着小鼠心肌中基础代谢和氧化损伤保护的重新编程。在小鼠心脏中显示的所有作用都是由于c9，t11 CLA而不是t10，c12 CLA。
Results from different trails have provided evidence of protective effects of cis-9,trans-11-conjugated linoleic acid (CLA) on cardiovascular diseases. But the inhibition of prolyl hydroxylase 1 (PHD1) associated with induction of hypoxia inducible factors (HIFs) by CLA in these protective effects has never been reported before. The objective of this study was to evaluate if the two predominant cis-9,trans-11 (c9, t11), trans-10,cis-12 (t10, c12) CLA isomers and mixture of these two isomers can inhibit PHD1 with induction of HIFs in myocardium in mice and subsequent effects on myocardium metabolism. CLA mixture and c9, t11 CLA inhibited PHD1 protein expression and increased the levels of protein and mRNA in HIF-2α in myocardium in mice. Meanwhile, CLA mixture and c9, t11 CLA also elevated the expression of HIF related transcriptional factors like PDK4 and PPARα. The reprogramming of basal metabolism in myocardium in mice was shown on increasing of GLUT4 gene expression by c9, t11 CLA supplemented group. UCP2 was increased by CLA mixture and c9, t11 CLA for attenuating production of ROS. CLA mixture and c9, t11 CLA could inhibit PHD1 and induce HIF-2α in myocardium in mice, which is associated with upregulation of PDK4 by activation of PPARα. This process also implies a reprogramming of basal metabolism and oxidative damage protection in myocardium in mice. All the effects shown in hearts of mice are due to c9, t11 CLA but not t10, c12 CLA.