Nrf2-dependent and Nrf2-independent induction of phase 2 detoxifying and antioxidant enzymes during keratinocyte differentiation
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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.
KeywordsPhase 2 detoxifying and antioxidant enzymes Keratinocyte Differentiation NF-E2 related factor-2
This research was supported by the High Value-Added Food Technology Development Program (109156-3), Ministry for Food, Agriculture, Forestry and Fisheries, Republic of Korea.
Conflict of interest
The authors state no conflict of interest.