title: Far-infrared therapy induces the nuclear translocation of PLZF which inhibits VEGF-induced proliferation in human umbilical vein endothelial cells.
abstract: 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.
authors.affiliation: Department of Internal Medicine, Taipei Medical University-Shuang Ho Hospital, New Taipei City, Taiwan.
authors.forename: Yung-Ho
authors.initials: YH
authors.lastname: Hsu
authors.forename: Yen-Cheng
authors.initials: YC
authors.lastname: Chen
authors.forename: Tso-Hsiao
authors.initials: TH
authors.lastname: Chen
authors.forename: Yuh-Mou
authors.initials: YM
authors.lastname: Sue
authors.forename: Tzu-Hurng
authors.initials: TH
authors.lastname: Cheng
authors.forename: Jia-Rung
authors.initials: JR
authors.lastname: Chen
authors.forename: Cheng-Hsien
authors.initials: CH
authors.lastname: Chen
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000528:radiation effects; D002467:Cell Nucleus / Q000378:metabolism* / Q000528:radiation effects; D049109:Cell Proliferation / Q000187:drug effects* / Q000528:radiation effects; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology / Q000528:radiation effects*; D006801:Humans; D007259:Infrared Rays / Q000627:therapeutic use*; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism*; D051058:Oncogene Protein v-akt / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010789:Phototherapy / Q000379:methods; D000075722:Promyelocytic Leukemia Zinc Finger Protein; D021381:Protein Transport / Q000528:radiation effects; D015398:Signal Transduction / Q000187:drug effects / Q000528:radiation effects; D015854:Up-Regulation / Q000528:radiation effects; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology*
chemical_list: D051741:Kruppel-Like Transcription Factors; D051058:Oncogene Protein v-akt; D019869:Phosphatidylinositol 3-Kinases; D000075722:Promyelocytic Leukemia Zinc Finger Protein; D042461:Vascular Endothelial Growth Factor A; C092037:ZBTB16 protein, human