Activation of caspases and apoptosis in response to low-voltage electric pulses
Activation of caspases and apoptosis in response to low-voltage electric pulses
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DOI：
10.3892/or_00000780
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发表时间：
2010-05-01
期刊：
影响因子：
4.2
通讯作者：
Yamaguchi, Takami
中科院分区：
文献类型：
--
作者：
Matsuki, Noriaki;Takeda, Motohiro;Yamaguchi, Takami
很少有研究探讨了低电压电脉冲（LVEPs）诱导的细胞凋亡。LVEP诱导低于膜击穿阈值的膜电位变化，并通过吞噬作用转运细胞外物质增加膜渗透性，而不发生电穿孔（孔形成）。我们证明，碘化丙啶的摄取和细胞凋亡的增加，根据在B16细胞，这表明在温和的电场条件下，相对较好的生存能力的LVEPs的持续时间和数量。我们发现LVEP诱导的细胞凋亡是通过caspase-8和caspase-9激活以及随后的caspase-3激活实现的。长时间LVEPs只造成轻微的细胞损伤，这样的细胞凋亡率（细胞凋亡/总细胞死亡）在电脉冲处理的细胞是类似于未处理的对照细胞。为了评估半胱天冬酶依赖性在LVEP诱导的细胞凋亡中的相对程度，使用泛半胱天冬酶抑制剂（Z-VAD-FMK）分析细胞凋亡率和半胱天冬酶-3活性。Z-VAD-FMK处理抑制，但没有取消。LVEP诱导的细胞凋亡，表明caspase-3以外的caspase参与这一途径。而且。LVEP治疗抑制细胞生长，表明LVEP治疗可能是一种有价值的抗癌疗法。虽然LVEP诱导的细胞凋亡的机制尚不清楚，但它可能与Ca 2+和其他参与caspase激活的细胞外物质的膜转运功能障碍有关。
Few studies have examined apoptosis induced by low-voltage electric pulses (LVEPs). LVEP-induce changes in membrane potential that are below the membrane breakdown threshold and increase membrane permeability without electroporation (pore formation) through the transport of extracellular substances via phagocytosis. We demonstrated that propidium iodide uptake and apoptosis increased in accordance with the duration and number of LVEPs in B16 cells, which showed relatively good viability under mild electric field conditions. We showed that LVEP-induced apoptosis was achieved through caspase-8 and -9 activation and subsequent caspase-3 activation. Long-duration LVEPs caused only mild cell damage, such that the apoptosis ratio (apoptosis/total cell death) in electric pulse-treated cells was similar to that in non-treated control cells. To assess the relative degree of caspase dependency in LVEP-induced apoptosis, the apoptosis rate and caspase-3 activity were analyzed using a pan-caspase inhibitor (Z-VAD-FMK). Z-VAD-FMK treatment inhibited, but did not abolish. LVEP-induced apoptosis, indicating that caspases other than caspase-3 participate in this pathway. Moreover. LVEP treatment inhibited cell growth, suggesting that LVEP treatment may be a valuable anticancer therapy. Although the mechanism of LVEP-induced apoptosis remains unclear, it may be related to dysfunctional membrane transport of Ca2+ and other extracellular substances involved in caspase activation.