Oral communication, CS12 / C52

Official XXIst International Pigment Cell Conference website - 21-24 Sept 2011, Bordeaux - France | updated: September 04 2011

Antioxydant defenses in human epidermal melanocytes and keratinocytes suggests that Nrf2 plays a peculiar role in epidermis: implication in vitiligo lesions

Melanin and its chemical intermediates can both generate and scavenge reactive species. Melanocyte have thus to manage a specific situation towards oxidative stress, especially when exposed to sunlight. For instance oxidative stress induced by UV radiation from a solar simulator (SSUV: 300-400 nm or UVA: 320-400 nm) in cultured human melanocytes was stronger when melanogenesis was stimulated. By comparing antioxidant status in human melanocytes and keratinocytes from same donors, we could show that: 1. reduced glutathione content was higher in keratinocytes, 2. basal expression of NQO1 (mRNA and protein) was higher in melanocytes, 3. when Nrf2 was stimulated (by sulforaphane, lipoïc acid or by silencing of Keap1), HO1 (mRNA and protein) and modulatory subunit of gamma-glutamyl-cysteine-ligase (GCLm, mRNA) were mainly induced in melanocytes whereas catalytic subunit of GCL (GCLc) was over expressed in keratinocytes, 4. in a microarray assay, HO1, ferritin, catalase as well as genes from NQO family or GST family displayed a stronger basal expression in melanocytes whereas genes from GPX family were mainly expressed in keratinocytes. Moreover, Nrf2, NQO1, GCLm and GCLc were up regulated in lesional epidermal skin of subjects with vitiligo, suggesting that redox balance is impaired in this disease. These data are of importance in order to better understand how Nrf2 is involved in skin in order to cope with environmental oxidative stress.

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