Department of Internal Medicine, Taipei Medical University-Shuang Ho Hospital, New Taipei City, Taiwan.
PLoS One. 2012;7(1):e30674. doi: 10.1371/journal.pone.0030674. Epub 2012 Jan 23.
Many studies suggest that far-infrared (FIR) therapy can reduce the frequency of some vascular-related diseases. The non-thermal effect of FIR was recently found to play a role in the long-term protective effect on vascular function, but its molecular mechanism is still unknown. In the present study, we evaluated the biological effect of FIR on vascular endothelial growth factor (VEGF)-induced proliferation in human umbilical vein endothelial cells (HUVECs). We found that FIR ranging 3∼10 µm significantly inhibited VEGF-induced proliferation in HUVECs. According to intensity and time course analyses, the inhibitory effect of FIR peaked at an effective intensity of 0.13 mW/cm(2) at 30 min. On the other hand, a thermal effect did not inhibit VEGF-induced proliferation in HUVECs. FIR exposure also inhibited the VEGF-induced phosphorylation of extracellular signal-regulated kinases in HUVECs. FIR exposure further induced the phosphorylation of endothelial nitric oxide (NO) synthase (eNOS) and NO generation in VEGF-treated HUVECs. Both VEGF-induced NO and reactive oxygen species generation was involved in the inhibitory effect of FIR. Nitrotyrosine formation significantly increased in HUVECs treated with VEGF and FIR together. Inhibition of phosphoinositide 3-kinase (PI3K) by wortmannin abolished the FIR-induced phosphorylation of eNOS and Akt in HUVECs. FIR exposure upregulated the expression of PI3K p85 at the transcriptional level. We further found that FIR exposure induced the nuclear translocation of promyelocytic leukemia zinc finger protein (PLZF) in HUVECs. This induction was independent of a thermal effect. The small interfering RNA transfection of PLZF blocked FIR-increased PI3K levels and the inhibitory effect of FIR. These data suggest that FIR induces the nuclear translocation of PLZF which inhibits VEGF-induced proliferation in HUVECs.
许多研究表明，远红外（FIR）治疗可以降低某些血管相关疾病的发病率。最近发现，FIR 的非热效应在血管功能的长期保护作用中发挥作用，但它的分子机制尚不清楚。在本研究中，我们评估了 FIR 对人脐静脉内皮细胞（HUVEC）中血管内皮生长因子（VEGF）诱导增殖的生物学效应。我们发现，FIR 在 3-10 µm 范围内显著抑制了 VEGF 诱导的 HUVEC 增殖。根据强度和时间过程分析，FIR 的抑制作用在 30 分钟时达到有效强度 0.13 mW/cm2 的峰值。另一方面，热效应不会抑制 HUVEC 中 VEGF 诱导的增殖。FIR 暴露还抑制了 VEGF 诱导的 HUVEC 中细胞外信号调节激酶的磷酸化。FIR 暴露进一步诱导了 VEGF 处理的 HUVEC 中内皮型一氧化氮合酶（eNOS）的磷酸化和 NO 的产生。FIR 的抑制作用涉及 VEGF 诱导的 NO 和活性氧的产生。与 VEGF 和 FIR 一起处理的 HUVEC 中硝基酪氨酸的形成明显增加。wortmannin 抑制磷酯酰肌醇 3-激酶（PI3K）完全消除了 FIR 诱导的 HUVEC 中 eNOS 和 Akt 的磷酸化。FIR 暴露在转录水平上调了 PI3K p85 的表达。我们进一步发现，FIR 暴露诱导了 HUVEC 中早幼粒细胞白血病锌指蛋白（PLZF）的核转位。这种诱导与热效应无关。PLZF 的小干扰 RNA 转染阻断了 FIR 增加的 PI3K 水平和 FIR 的抑制作用。这些数据表明，FIR 诱导了 PLZF 的核转位，从而抑制了 HUVEC 中 VEGF 诱导的增殖。
