Regulation of ultraviolet B radiation-mediated activation of AP1 signaling by retinoids in primary keratinocytes

Nadine Darwiche, Hisham Bazzi, Lara El-Touni, Ghada Abou-Lteif, Rami Doueiri, Asma Hatoum, Samar Maalouf, Hala Gali-Muhtasib

Research output: Contribution to journalArticlepeer-review


The main cause of skin cancer and photo-aging is chronic exposure to ultraviolet B (UVB) radiation. Such damage can be ameliorated by retinoid treatment. UVB-radiation-induced skin carcinogenesis is associated with the induction of activator protein 1 (AP1) signaling and factors, namely FOS and JUN family members. We investigated the effects of several retinoids, all-trans-retinoic acid (tRA), 9-cis-retinoic acid (cRA), and N-(4-hydroxyphenyl)-retinamide (HPR), on UVB-induced damage in primary mouse keratinocytes. In addition, the interplay between UVB radiation, retinoid receptors, and AP1 signaling was assessed using Western blot analysis and ribonuclease protection and gene reporter assays. Exposure of keratinocytes to UVB radiation caused a down-regulation of the retinoid receptor protein levels in a proteasome-mediated manner. In contrast, FOS and JUN proteins were transiently induced shortly after exposure to UVB radiation. Retinoid treatment caused a dose-dependent reduction in the levels of retinoid receptor proteins. When irradiated cells were treated with retinoids, no significant effects on API protein expression were noted. Interestingly, pretreatments with tRA and cRA, but not HPR, suppressed UVB-radiation-induced AP1 activity by more than 50%, whereas post-treatment failed to produce similar effects. Our findings indicate that the inhibition of AP1 activity by retinoids explains, at least in part, the chemopreventive potential of retinoids in UV-radiation-associated epidermal damage.

Original languageEnglish (US)
Pages (from-to)296-306
Number of pages11
JournalRadiation Research
Issue number3
StatePublished - Mar 2005
Externally publishedYes

ASJC Scopus subject areas

  • Biophysics
  • Radiation
  • Radiology Nuclear Medicine and imaging


Dive into the research topics of 'Regulation of ultraviolet B radiation-mediated activation of AP1 signaling by retinoids in primary keratinocytes'. Together they form a unique fingerprint.

Cite this