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Am J Physiol Cell Physiol (September 4, 2002). doi:10.1152/ajpcell.00205.2002
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Articles in PresS, published online ahead of print September 4, 2002
Am J Physiol Cell Physiol, 10.1152/ajpcell.00205.2002
Submitted on May 3, 2002
Accepted on August 27, 2002

Ultraviolet A radiation transiently disrupts gap junctional communication in human keratinocytes

Nicolas Provost1, Marielle Moreau2, Armelle Leturque3*, and Carine Nizard2

1 Laboratoire de Pharmacologie Cellulaire, Ecole Pratique des Hautes Etudes HE, Paris, France
2 Laboratoire de Pharmacologie Cellulaire, Ecole Pratique des Hautes Etudes HE, Paris, France; Perfumes and Cosmetics Division, LVMH, Saint Jean De Bray, France
3 U505, INSERM, Paris, France

* To whom correspondence should be addressed. E-mail: leturque{at}infobiogen.fr.

Ultraviolet A (UVA) (320-400 nm) radiation is known to cause cutaneous aging and skin cancer. We studied the effect of UVA (365 nm) radiation on the human epidermis by focusing on keratinocyte gap junction-mediated intercellular communication (GJIC). We observed a dose-dependent 10-fold decrease in GJIC induced by UVA in normal human keratinocytes. This decrease in GJIC was associated with time-dependent internalization of connexin43 (Cx43). UVA radiation also damaged the actin cytoskeleton, as shown by microfilament disappearance. Importantly, the decrease in GJIC was transient when keratinocytes were irradiated with 10 J/cm2 UVA, with a return to baseline values after 8 hours. Concomitantly, Cx43 was re-localized and the actin cytoskeleton was restored. UVA irradiation and 12-O-tetradecanoylphorbol-13-acetate (TPA) treatment activated protein kinase-C and reduced GJIC. However, Cx43 localization and phosphorylation were differently regulated by the two treatments. This suggests that at least two different pathways may mediate the observed fall in GJIC. These findings identify keratinocyte gap-junction-mediated-intercellular-communication as a new UVA target, which might sensitize human skin to photoaging and cancer formation.




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