Systemic administration of the apocarotenoid bixin protects skin against solar UV-induced damage through activation of NRF2

Shasha Tao, Sophia L. Park, Montserrat Rojo De La Vega, Donna Zhang, Georg T Wondrak

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Exposure to solar ultraviolet (UV) radiation is a causative factor in skin photodamage and carcinogenesis, and an urgent need exists for improved molecular photoprotective strategies different from (or synergistic with) photon absorption. Recent studies suggest a photoprotective role of cutaneous gene expression orchestrated by the transcription factor NRF2 (nuclear factor-E2-related factor 2). Here we have explored the molecular mechanism underlying carotenoid-based systemic skin photoprotection in SKH-1 mice and provide genetic evidence that photoprotection achieved by the FDA-approved apocarotenoid and food additive bixin depends on NRF2 activation. Bixin activates NRF2 through the critical Cys-151 sensor residue in KEAP1, orchestrating a broad cytoprotective response in cultured human keratinocytes as revealed by antioxidant gene expression array analysis. Following dose optimization studies for cutaneous NRF2 activation by systemic administration of bixin, feasibility of bixin-based suppression of acute cutaneous photodamage from solar UV exposure was investigated in Nrf2+/+ versus Nrf2-/- SKH-1 mice. Systemic administration of bixin suppressed skin photodamage, attenuating epidermal oxidative DNA damage and inflammatory responses in Nrf2+/+ but not in Nrf2-/- mice, confirming the NRF2-dependence of bixin-based cytoprotection. Taken together, these data demonstrate feasibility of achieving NRF2-dependent cutaneous photoprotection by systemic administration of the apocarotenoid bixin, a natural food additive consumed worldwide.

Original languageEnglish (US)
Pages (from-to)690-700
Number of pages11
JournalFree Radical Biology and Medicine
Volume89
DOIs
StatePublished - Dec 1 2015

Fingerprint

NF-E2-Related Factor 2
Skin
Chemical activation
Food additives
Food Additives
Gene expression
Gene Expression
Cytoprotection
Carotenoids
bixin
Solar radiation
Keratinocytes
Photons
Ultraviolet radiation
DNA Damage
Carcinogenesis
Transcription Factors
Antioxidants
Radiation
DNA

Keywords

  • Antioxidant gene expression
  • Bixin
  • NRF2
  • Skin photodamage
  • Systemic photoprotection

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

Cite this

Systemic administration of the apocarotenoid bixin protects skin against solar UV-induced damage through activation of NRF2. / Tao, Shasha; Park, Sophia L.; De La Vega, Montserrat Rojo; Zhang, Donna; Wondrak, Georg T.

In: Free Radical Biology and Medicine, Vol. 89, 01.12.2015, p. 690-700.

Research output: Contribution to journalArticle

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