Kawano Ayumi, Hayakawa Akimitsu, Kojima Shuji, Tsukimoto Mitsutoshi, Sakamoto Hikaru
Radioisotope Research Laboratory, School of Pharmacy, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo, Japan.
Department of Radiation Biosciences, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda-shi, Chiba, Japan.
Toxicol Rep. 2015 Feb 7;2:391-400. doi: 10.1016/j.toxrep.2015.01.015. eCollection 2015.
Ultraviolet A (UVA) radiation, the major UV component of solar radiation, can penetrate easily to the dermis, where it causes significant damage to cellular components by inducing formation of reactive oxygen species (ROS). On the other hand, extracellular ATP is released in response to various stimuli, and activates purinergic P2X7 receptor, triggering ROS production and cell death. Here, we examined the hypothesis that ATP release followed by activation of P2X7 receptor plays a role in UVA-induced oxidative cell damage, using human acute monocytic leukemia cell line THP-1. Indeed, UVA irradiation of THP-1 cells induced ATP release and activation of P2X7 receptor. Irradiated cells showed a rapid increase of both p67 in membrane fraction and intracellular ROS. Pretreatment with ecto-nucleotidase or P2X7 receptor antagonist blocked the UVA-initiated membrane translocation of p67 and ROS production. Furthermore, pretreatment with antioxidant or P2X7 receptor antagonist efficiently protected UVA-irradiated cells from caspase-dependent cell death. These findings show that autocrine signaling through release of ATP and activation of P2X7 receptor is required for UVA-induced stimulation of oxidative stress in monocytes.
紫外线A（UVA）辐射是太阳辐射的主要紫外线成分，它能够轻易穿透至真皮层，在真皮层中，它通过诱导活性氧（ROS）的形成对细胞成分造成显著损伤。另一方面，细胞外ATP会响应各种刺激而释放，并激活嘌呤能P2X7受体，触发ROS生成和细胞死亡。在此，我们使用人急性单核细胞白血病细胞系THP-1检验了以下假说：ATP释放后激活P2X7受体在UVA诱导的氧化性细胞损伤中起作用。事实上，对THP-1细胞进行UVA照射会诱导ATP释放并激活P2X7受体。受照射细胞的膜组分中p67和细胞内ROS均迅速增加。用外切核苷酸酶或P2X7受体拮抗剂预处理可阻断UVA引发的p67膜转位和ROS生成。此外，用抗氧化剂或P2X7受体拮抗剂预处理可有效保护UVA照射的细胞免于半胱天冬酶依赖性细胞死亡。这些发现表明，通过ATP释放和P2X7受体激活的自分泌信号传导是UVA诱导单核细胞氧化应激刺激所必需的。
