title: Differentiation-dependent expression of NADP(H):quinone oxidoreductase-1 via NF-E2 related factor-2 activation in human epidermal keratinocytes.
abstract: BACKGROUND
  NADP(H):quinone oxidoreductase-1 (NQO-1) is known for its protective role in skin carcinogenesis, but the expression of NQO-1 during keratinocyte (KC) differentiation has not been studied.
  
  
  OBJECTIVE
  The purpose of the current study was to evaluate modulation of NQO-1 and NF-E2-related factor-2 (Nrf2) during KC differentiation.
  
  
  METHODS
  Normal human epidermal keratinocytes (NHEKs) were induced to differentiation by prolonged culture after confluency (postconfluence).
  
  
  RESULTS
  NQO-1 was induced at the late stage of differentiation of NHEKs (7th day of postconfluence). The expression of postconfluence-induced NQO-1 was stimulated by 0.1 mM H(2)O(2), but attenuated by 5 mM N-acetylcysteine, implying that reactive oxygen species (ROS) are implicated in the expression of NQO-1 in differentiated KCs. Nrf2 was up-regulated at the earlier than NQO-1 induction (3rd day of postconfluence). The Nrf2-dependent expression of NQO-1 was further supported by Nrf2-siRNA experiments. A confocal study confirmed the differentiation-dependent induction and activation of NOQ-1 and Nrf-2 in NHEKs. Immunohistochemistry showed that NQO-1 was accentuated in the upper epidermal layers, supporting the notion that differentiation-dependent NQO-1 expression is functional in human skin in vivo.
  
  
  CONCLUSIONS
  These results demonstrate that NQO-1 is modulated during KC differentiation via Nrf2 pathway, suggesting the active role of NQO-1 in the differentiating epidermis.
authors.affiliation: Department of Dermatology, Chonnam National University Medical School, Gwangju, Republic of Korea.
authors.forename: Mei Shan
authors.initials: MS
authors.lastname: Piao
authors.forename: Jee-Young
authors.initials: JY
authors.lastname: Choi
authors.forename: Dong-Ho
authors.initials: DH
authors.lastname: Lee
authors.forename: Sook Jung
authors.initials: SJ
authors.lastname: Yun
authors.forename: Jee-Bum
authors.initials: JB
authors.lastname: Lee
authors.forename: Seung-Chul
authors.initials: SC
authors.lastname: Lee
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D004817:Epidermis / Q000201:enzymology*; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007150:Immunohistochemistry / Q000379:methods; D015603:Keratinocytes / Q000166:cytology*; D018613:Microscopy, Confocal / Q000379:methods; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000096:biosynthesis* / Q000737:chemistry; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D017382:Reactive Oxygen Species; D014162:Transfection
chemical_list: D051267:NF-E2-Related Factor 2; D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide; D016660:NAD(P)H Dehydrogenase (Quinone); D000111:Acetylcysteine