UV-B induced alteration in purinergic receptors and signaling on HaCaT keratinocytes

Although there are a number of recognized risk factors resulting in cutaneous malignancies, very little is known about the exact mechanism. In keratinocytes different purinergic receptors have been implicated to play essential roles in deciding the fate of the cells through regulating proliferation and differentiation. While P2Y receptors seem to control the former, P2X receptors, among which the P2X7 receptor is associated with the induction of apoptosis, are likely to be responsible for the latter. Forty mJ/cm2 UV-B irradiation decreased the number of viable cells as assessed using MTT assay. This irradiation decreased the amount of both P2X1 and P2Y2 receptors and essentially destroyed the P2X7 receptors in surviving cells. Morphology of ATP-induced Ca2+ transients were altered in irradiated cells compared to control. The amplitude and the rate of rise of the transients were decreased and the return to resting [Ca2+]i prolonged. This observation is consistent with the finding that in control cells mostly ionotropic, while in irradiated cells mostly metabotropic receptors were underlying the response to ATP. These alterations in the expression pattern of purinergic receptors and in the Ca2+ transients could explain the observed decreased tendency for ATP-induced apoptosis and possibly contribute to the malignant transformation of keratinocytes.

► Expression pattern of P2X and P2Y receptor is changed by UV-B irradiation.
► P2X1, P2Y2 and P2X7 receptors were destroyed in irradiated cells.
► ATP-induced Ca2+ transients were altered in irradiated cells compared to control.
► Irradiated cells had decreased tendency for ATP-induced apoptosis.