Ultraviolet A radiation transiently disrupts gap junctional communication in human keratinocytes

Ultraviolet A (UVA) (320-400 nm)radiation is known to cause cutaneous aging and skin cancer. We studiedthe effect of UVA (365 nm) radiation on the human epidermis by focusingon keratinocyte gap junction-mediated intercellular communication(GJIC). We observed a dose-dependent 10-fold decrease in GJIC inducedby UVA in normal human keratinocytes. This decrease in GJIC wasassociated with time-dependent internalization of connexin43 (Cx43).UVA radiation also damaged the actin cytoskeleton, as shown bymicrofilament disappearance. Importantly, the decrease in GJIC wastransient when keratinocytes were irradiated with 10 J/cm²UVA, with a return to baseline values after 8 h. Concomitantly, Cx43 was relocalized and the actin cytoskeleton was restored. UVAirradiation and 12-O-tetradecanoylphorbol 13-acetate (TPA) treatment activated protein kinase C and reduced GJIC. However, Cx43localization and phosphorylation were differently regulated by the twotreatments. This suggests that at least two different pathways maymediate the observed fall in GJIC. These findings identify keratinocyteGJIC as a new UVA target that might sensitize human skin to photoagingand cancer formation.