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首页> 外文期刊>Biochemistry and Biophysics Reports >Adult human dermal fibroblasts exposed to nanosecond electrical pulses exhibit genetic biomarkers of mechanical stress
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Adult human dermal fibroblasts exposed to nanosecond electrical pulses exhibit genetic biomarkers of mechanical stress

机译：暴露于纳秒级电脉冲的成年人类真皮成纤维细胞显示出机械应激的遗传生物标记

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Background Exposure of cells to very short (1 μs) electric pulses in the megavolt/meter range have been shown to cause a multitude of effects, both physical and molecular in nature. Physically, nanosecond electrical pulses (nsEP) can cause disruption of the plasma membrane, cellular swelling, shrinking and blebbing. Molecularly, nsEP have been shown to activate signaling pathways, produce oxidative stress, stimulate hormone secretion and induce both apoptotic and necrotic death. We hypothesize that studying the genetic response of primary human dermal fibroblasts exposed to nsEP, will gain insight into the molecular mechanism(s) either activated directly by nsEP, or indirectly through electrophysiology interactions. Methods Microarray analysis in conjunction with quantitative real time polymerase chain reaction (qRT-PCR) was used to screen and validate genes selectively upregulated in response to nsEP exposure. Results Expression profiles of 486 genes were found to be significantly changed by nsEP exposure. 50% of the top 20 responding genes coded for proteins located in two distinct cellular locations, the plasma membrane and the nucleus. Further analysis of five of the top 20 upregulated genes indicated that the HDFa cells’ response to nsEP exposure included many elements of a mechanical stress response. Conclusions We found that several genes, some of which are mechanosensitive, were selectively upregulated due to nsEP exposure. This genetic response appears to be a primary response to the stimuli and not a secondary response to cellular swelling. General significance This work provides strong evidence that cells exposed to nsEP interpret the insult as a mechanical stress. Highlights ? Global gene expression analysis was performed on primary cells exposed to nsEP. ? The bioeffects of nsEP on adult human dermal fibroblasts were investigated. ? Microarray analysis suggests nsEP imparts a mechanical stress on cells. ? FOS, NR4A2, ITPKB, KLHL24, and SOD2 were upregulated in response to nsEP.
机译：背景技术已经证明，将电池暴露于兆伏/米范围内的非常短的（<1μs）电脉冲中会引起多种物理和分子效应。从物理上讲，纳秒电脉冲（nsEP）会导致质膜破裂，细胞肿胀，收缩和起泡。在分子上，已证明nsEP可激活信号传导途径，产生氧化应激，刺激激素分泌并诱导凋亡性和坏死性死亡。我们假设研究暴露于nsEP的人类原始皮肤成纤维细胞的遗传反应，将深入了解被nsEP直接激活或通过电生理相互作用间接激活的分子机制。方法使用微阵列分析结合定量实时聚合酶链反应（qRT-PCR）来筛选和验证响应nsEP暴露而选择性上调的基因。结果发现nsEP暴露可明显改变486个基因的表达谱。前20个响应基因中有50％编码位于两个不同细胞位置（质膜和细胞核）的蛋白质。对前20个上调基因中的5个的进一步分析表明，HDFa细胞对nsEP暴露的反应包括机械应激反应的许多因素。结论我们发现由于nsEP暴露，选择性地上调了几个基因，其中一些是机械敏感的。这种遗传反应似乎是对刺激的主要反应，而不是对细胞肿胀的次要反应。一般意义这项工作提供了有力的证据，表明暴露于nsEP的细胞将这种损伤解释为机械应力。强调 ？对暴露于nsEP的原代细胞进行全局基因表达分析。 ？研究了nsEP对成年人类皮肤成纤维细胞的生物作用。 ？微阵列分析表明，nsEP会对细胞施加机械应力。 ？响应nsEP，FOS，NR4A2，ITPKB，KLHL24和SOD2上调。

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