Cold atmospheric-pressure nitrogen plasma induces the production of reactive nitrogen species and cell death by increasing intracellular calcium in HEK293T cells
Cold atmospheric-pressure nitrogen plasma induces the production of reactive nitrogen species and cell death by increasing intracellular calcium in HEK293T cells
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DOI：
10.1016/j.abb.2018.07.015
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发表时间：
2018-09-15
影响因子：
3.9
通讯作者：
Hisatomi, Hisashi
中科院分区：
文献类型：
--
作者：
Iuchi, Katsuya;Morisada, Yukina;Hisatomi, Hisashi
冷大气压等离子体（CAP）近年来已成为一种有前途的癌症治疗工具。在这项研究中，我们使用了一个CAP设备与氮气（N（2）CAP）和研究的影响，N（2）CAP对培养细胞的活力。此外，我们研究了培养基中N（2）CAP产生的过氧化氢（H2 O2）是否参与了N（2）CAP诱导的细胞死亡。在此，我们发现N（2）CAP辐射抑制人胚肾细胞系HEK 293 T的细胞增殖，并且N（2）CAP以辐射时间和距离依赖的方式诱导细胞死亡。此外，N（2）CAP和H2 O2还能增加HEK 293 T细胞内钙离子水平，并诱导caspase-3/7活化。N（2）CAP辐射诱导PBS或培养基中H2 O2和亚硝酸盐/硝酸盐的产生具有时间依赖性。然而，N（2）CAP照射后溶液中H2 O2的含量太低，无法诱导细胞死亡。有趣的是，羧基PTIO，一氧化氮清除剂，或BAPTA-AM，细胞渗透性钙螯合剂，抑制N（2）CAP诱导的形态学变化和细胞死亡。这些结果表明，活性氮的产生和细胞内钙的增加参与了N（2）CAP诱导的细胞死亡。
Cold atmospheric-pressure plasma (CAP) has been emerging as a promising tool for cancer therapy in recent times. In this study, we used a CAP device with nitrogen gas (N(2)CAP) and investigated the effect of the N(2)CAP on the viability of cultured cells. Moreover, we investigated whether N(2)CAP-produced hydrogen peroxide (H2O2) in the medium is involved in N(2)CAP-induced cell death. Here, we found that the N(2)CAP irradiation inhibited cell proliferation in the human embryonic kidney cell line HEK293T and that the N(2)CAP induced cell death in an irradiation time- and distance-dependent manner. Furthermore, the N(2)CAP and H2O2 increased intracellular calcium levels and induced caspase-3/7 activation in HEK293T cells. The N(2)CAP irradiation induced a time dependent production of H2O2 and nitrite/nitrate in PBS or culture medium. However, the amount of H2O2 in the solution after N(2)CAP irradiation was too low to induce cell death. Interestingly, carboxy-PTIO, a nitric oxide scavenger, or BAPTA-AM, a cell-permeable calcium chelator, inhibited N(2)CAP-induced morphological change and cell death. These results suggest that the production of reactive nitrogen species and the increase in intracellular calcium were involved in the N(2)CAP-induced cell death.