Frank Sandra, Menezes Salatiel, Lebreton-De Coster Corinne, Oster Michèle, Dubertret Louis, Coulomb Bernard
INSERM U532, Institut de Recherche sur la Peau, Pavillon Bazin, Hôpital Saint-Louis, Paris, France.
Exp Dermatol. 2006 Feb;15(2):130-7. doi: 10.1111/j.1600-0625.2005.00397.x.
We have previously observed that preirradiation with naturally occurring doses of near-infrared (IR) protects normal human dermal fibroblasts from ultraviolet (UV) cytotoxicity in vitro. This effect was observed in temperature-controlled conditions, without heat shock protein (Hsp72-70) induction. Moreover, IR inhibited UVB-induced apoptosis by modulating the Bcl2/Bax balance, pointing to a role of p53. Here, we show for the first time that p53-deficient SaOs cells are not protected from UVB cytotoxicity by IR preirradiation, suggesting that the response to IR is p53-dependent. Thus, we investigated the effect of IR on the p53 signaling pathway. Normal human dermal fibroblasts exposed in vitro to IR accumulated p53 protein, involving p53 stabilization and phosphorylation of serine 15 (Ser15) and Ser20. IR-induced p53 accumulation correlated with increased expression of p21 and GADD45, showing that IR also stimulates p53 transcriptional activity. By modulating UVB-induced targets of the p53 signaling pathway, IR irradiation appears to anticipate the UVB response and to prepare cells to better resist subsequent UV-induced stress. This is reinforced by the fact that IR preirradiation reduces the formation of UVB-induced thymine dimers.
我们之前观察到，用自然剂量的近红外光（IR）进行预照射可在体外保护正常人皮肤成纤维细胞免受紫外线（UV）的细胞毒性作用。在温度受控的条件下观察到了这种效应，且未诱导热休克蛋白（Hsp72 - 70）。此外，IR通过调节Bcl2/Bax平衡抑制UVB诱导的细胞凋亡，这表明p53发挥了作用。在此，我们首次表明，p53缺陷的SaOs细胞不能通过IR预照射免受UVB的细胞毒性作用，这表明对IR的反应是p53依赖性的。因此，我们研究了IR对p53信号通路的影响。体外暴露于IR的正常人皮肤成纤维细胞积累了p53蛋白，这涉及p53的稳定以及丝氨酸15（Ser15）和丝氨酸20（Ser20）的磷酸化。IR诱导的p53积累与p21和GADD45表达的增加相关，表明IR还刺激了p53的转录活性。通过调节UVB诱导的p53信号通路靶点，IR照射似乎预先引发了UVB反应，并使细胞做好更好地抵抗后续UV诱导应激的准备。IR预照射减少了UVB诱导的胸腺嘧啶二聚体的形成，这一事实进一步强化了上述观点。
