title: DJ-1/park7 modulates vasorelaxation and blood pressure via epigenetic modification of endothelial nitric oxide synthase.
abstract: OBJECTIVE
  DJ-1/park7, a multifunctional protein, may play essential roles in the vascular system. However, the function of DJ-1/park7 in vascular contractility has remained unclear. The present study was designed to investigate whether the DJ-1/park7 is involved in the regulation of vascular contractility and systolic blood pressure (SBP).
  
  
  RESULTS
  Norepinephrine (NE) elevated contraction in endothelium-intact vessels in a dose-dependent manner, to a greater extent in DJ-1/park7 knockout (DJ-1/park7(-/-)) mice than in wild-type (DJ-1/park7(+/+)) mice. Acetylcholine inhibited NE-evoked contraction in endothelium-intact vessels, and this was markedly impaired in DJ-1/park7(-/-) mice compared with DJ-1/park7(+/+). Nitric oxide (NO) production (82.1 ± 2.8% of control) and endothelial NO synthase (eNOS) expression (61.7 ± 8.9%) were lower, but H2O2 production (126.4 ± 8.6%) was higher, in endothelial cells from DJ-1/park7(-/-) mice than in those from DJ-1/park7(+/+) controls; these effects were reversed by DJ-1/park7-overexpressing endothelial cells from DJ-1/park7(-/-) mice. Histone deacetylase (HDAC)-1 recruitment and H3 histone acetylation at the eNOS promoter were elevated and diminished, respectively, in DJ-1/park7(-/-) mice compared with DJ-1/park7(+/+) controls. Moreover, SBP was significantly elevated in DJ-1/park7(-/-) mice compared with DJ-1/park7(+/+) controls, but this elevation was inhibited in mice treated with valproic acid, an inhibitor of Class I HDACs including HDAC-1.
  
  
  CONCLUSIONS
  These results demonstrate that DJ-1/park7 protein may be implicated in the regulation of vascular contractility and blood pressure, probably by the impairment of NO production through H2O2-mediated epigenetic inhibition of eNOS expression.
authors: Department of Physiology, Institute of Functional Genomics, School of Medicine, Konkuk University, 322 Danwol-dong, Chungju 380-701, South Korea.
authors: Kyung Jong
authors: KJ
authors: Won
authors: Seung Hyo
authors: SH
authors: Jung
authors: Soo Hyun
authors: SH
authors: Jung
authors: Kang Pa
authors: KP
authors: Lee
authors: Hwan Myung
authors: HM
authors: Lee
authors: Dong-Youb
authors: DY
authors: Lee
authors: Eun-Seok
authors: ES
authors: Park
authors: Junghwan
authors: J
authors: Kim
authors: Bokyung
authors: B
authors: Kim
mesh_terms: D000818:Animals; D001794:Blood Pressure; D004730:Endothelium, Vascular / Q000378:metabolism*; D044127:Epigenesis, Genetic / Q000235:genetics / Q000502:physiology*; D006861:Hydrogen Peroxide / Q000378:metabolism; D008297:Male; D051379:Mice; D009569:Nitric Oxide / Q000096:biosynthesis; D052250:Nitric Oxide Synthase Type III / Q000235:genetics* / Q000378:metabolism; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D054464:Peroxiredoxins; D000071617:Protein Deglycase DJ-1; D014664:Vasodilation / Q000235:genetics / Q000502:physiology
chemical_list: D015513:Oncogene Proteins; D009569:Nitric Oxide; D006861:Hydrogen Peroxide; D054464:Peroxiredoxins; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse; C503466:PARK7 protein, mouse; D000071617:Protein Deglycase DJ-1
keywords: DJ-1/park7; Epigenetic modification; Vascular contractility; eNOS