The oxidative molecular regulation mechanism of NOX in children with phenylketonuria

Int J Dev Neurosci. 2014 Nov:38:178-83. doi: 10.1016/j.ijdevneu.2014.09.002. Epub 2014 Sep 29.


Phenylketonuria (PKU) is the most frequent inherited disorder of amino acid metabolism. In our previous work, we investigated the role of NADPH oxidase (NOX) in a Pahenu2-BTBR PKU mouse model, and an in vitro cell culture model of PKU. In the current study, we evaluated various oxidative stress parameters, namely total antioxidant capacity (T-AOC), glutathione (GSH) and maleic dialdehyde (MDA) in the plasma of 40 PKU children, for further investigating the oxidative molecular regulation mechanism of NOX in PKU. It was observed that T-AOC and GSH markedly decreased in PKU as compared with the control group (P<0.01), and seemed to correlate negatively with Phe level. However, there was no statistical difference in MDA level among the three groups. And 8-isoprostane in the blood samples of PKU2 groups was slightly higher than control group (P<0.05). Additionally, mRNA levels of subunits of NOX included p47(phox) and p67(phox) significantly increased in PKU group (P<0.01). These results reflected that NOX is the important source of reactive oxygen species and is involved in the oxidative molecular regulation mechanism in PKU, which shows a new perspective toward understanding the biological underpinnings of PKU.

Keywords: Children; NOX; Oxidative stress; Phenylketonuria (PKU); Superoxide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aldehydes / metabolism
  • Analysis of Variance
  • Apoptosis
  • Child
  • Child, Preschool
  • Dinoprost / analogs & derivatives
  • Dinoprost / blood
  • Female
  • Flow Cytometry
  • Glutathione / genetics
  • Glutathione / metabolism
  • Humans
  • Infant
  • Infant, Newborn
  • Leukocytes, Mononuclear / metabolism*
  • Male
  • NADPH Oxidases / blood*
  • NADPH Oxidases / genetics
  • Phenylketonurias / blood*
  • Phenylketonurias / pathology*
  • RNA, Messenger / metabolism


  • Aldehydes
  • RNA, Messenger
  • malealdehyde
  • 8-epi-prostaglandin F2alpha
  • Dinoprost
  • NADPH Oxidases
  • Glutathione