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The nuclear factor (erythroid‐derived 2)‐like 2 ( NRF 2) antioxidant response promotes melanocyte viability and reduces toxicity of the vitiligo‐inducing phenol monobenzone
Author(s) -
Arowojolu Omotayo A.,
Orlow Seth J.,
Elbuluk Nada,
Manga Prashiela
Publication year - 2017
Publication title -
experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 96
eISSN - 1600-0625
pISSN - 0906-6705
DOI - 10.1111/exd.13350
Subject(s) - vitiligo , melanocyte , oxidative stress , viability assay , toxicity , keap1 , gene knockdown , antioxidant , biology , cancer research , chemistry , pharmacology , endocrinology , medicine , immunology , melanoma , biochemistry , transcription factor , apoptosis , gene
Vitiligo, characterised by progressive melanocyte death, can be initiated by exposure to vitiligo‐inducing phenols ( VIP s). VIP s generate oxidative stress in melanocytes and activate the master antioxidant regulator NRF 2. While NRF 2‐regulated antioxidants are reported to protect melanocytes from oxidative stress, the role of NRF 2 in the melanocyte response to monobenzone, a clinically relevant VIP , has not been characterised. We hypothesised that activation of NRF 2 may protect melanocytes from monobenzone‐induced toxicity. We observed that knockdown of NRF 2 or NRF 2‐regulated antioxidants NQO 1 and PRDX 6 reduced melanocyte viability, but not viability of keratinocytes and fibroblasts, suggesting that melanocytes were preferentially dependent upon NRF 2 activity for growth compared to other cutaneous cells. Furthermore, melanocytes activated the NRF 2 response following monobenzone exposure and constitutive NRF 2 activation reduced monobenzone toxicity, supporting NRF 2's role in the melanocyte stress response. In contrast, melanocytes from individuals with vitiligo (vitiligo melanocytes) did not activate the NRF 2 response as efficiently. Dimethyl fumarate‐mediated NRF 2 activation protected normal and vitiligo melanocytes against monobenzone‐induced toxicity. Given the contribution of oxidant‐antioxidant imbalance in vitiligo, modulation of this pathway may be of therapeutic interest.

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