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01-07-2012 | Original Paper

Nrf2-dependent and Nrf2-independent induction of phase 2 detoxifying and antioxidant enzymes during keratinocyte differentiation

Authors: Mei Shan Piao, Jae-Jeong Park, Jee-Young Choi, Dong-Hoon Lee, Sook Jung Yun, Jee-Bum Lee, Seung-Chul Lee

Published in: Archives of Dermatological Research | Issue 5/2012

Abstract

As antioxidant enzymes can be actively modulated during keratinocyte (KC) differentiation, this study was aimed to evaluate the modulation of a group of phase 2 detoxifying and antioxidant enzymes (phase 2 enzymes) during KC differentiation. In postconfluence-induced differentiation model of KC, heme oxygenase-1 (HO-1), NADP(H):quinone oxidoreductase-1 (NQO-1), and glutathione S-transferase pi (GSTpi) were up-regulated at a transcriptional level. In Western blot analysis, the phase 2 enzymes were up-regulated by H₂O₂, but down-regulated by N-acetyl cysteine, indicating the active role of reactive oxygen species for their expression during KC differentiation. When a redox-sensitive NF-E2 related factor-2 (Nrf2), a key transcriptional factor for phase 2 enzymes, was knocked down by small interfering RNA transfection in differentiated KCs, only NQO-1 was down-regulated in both mRNA and protein levels. In human skin, expression levels of the phase 2 enzymes were up-regulated in the differentiated KC in the normal epidermis and keratotic foci in squamous cell carcinoma, further supporting the differentiation-dependent expression of phase 2 enzymes in vivo. This study demonstrates that a group of phase 2 enzymes are modulated during KC differentiation via either Nrf2-dependent (NQO-1) or Nrf2-independent (HO-1 and GSTpi) ways.

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Title: Nrf2-dependent and Nrf2-independent induction of phase 2 detoxifying and antioxidant enzymes during keratinocyte differentiation
Authors: Mei Shan Piao
Jae-Jeong Park
Jee-Young Choi
Dong-Hoon Lee
Sook Jung Yun
Jee-Bum Lee
Seung-Chul Lee
Publication date: 01-07-2012
Publisher: Springer-Verlag
Published in: Archives of Dermatological Research / Issue 5/2012
Print ISSN: 0340-3696
Electronic ISSN: 1432-069X
DOI: https://doi.org/10.1007/s00403-012-1215-7

At a glance: The STEP trials

Springer Medicine

Nrf2-dependent and Nrf2-independent induction of phase 2 detoxifying and antioxidant enzymes during keratinocyte differentiation

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

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