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Caveolin-1 is Involved in Regulating the Biological Response of Cells to Nanosecond Pulsed Electric Fields
The Journal of Membrane Biology ( IF 2.4 ) Pub Date : 2021-01-11 , DOI: 10.1007/s00232-020-00160-z
Jody C Cantu 1 , Gleb P Tolstykh 1 , Melissa Tarango 1 , Hope T Beier 2 , Bennett L Ibey 3
Affiliation  

Abstract

Nanosecond pulsed electric fields (nsPEFs) induce changes in the plasma membrane (PM), including PM permeabilization (termed nanoporation), allowing free passage of ions into the cell and, in certain cases, cell death. Recent studies from our laboratory show that the composition of the PM is a critical determinant of PM nanoporation. Thus, we hypothesized that the biological response to nsPEF exposure could be influenced by lipid microdomains, including caveolae, which are specialized invaginations of the PM that are enriched in cholesterol and contain aggregates of important cell signaling proteins, such as caveolin-1 (Cav1). Caveolae play a significant role in cellular signal transduction, including control of calcium influx and cell death by interaction of Cav1 with regulatory signaling proteins. Present results show that depletion of Cav1 increased the influx of calcium, while Cav1 overexpression produced the opposite effect. Additionally, Cav1 is known to bind and sequester important cell signaling proteins within caveolae, rendering the binding partners inactive. Imaging of the PM after nsPEF exposure showed localized depletion of PM Cav1 and results of co-immunoprecipitation studies showed dissociation of two critical Cav1 binding partners (transient receptor potential cation channel subfamily C1 (TRPC1) and inositol trisphosphate receptor (IP3R)) after exposure to nsPEFs. Release of TRPC1 and IP3R from Cav1 would activate downstream signaling cascades, including store-operated calcium entry, which could explain the influx in calcium after nsPEF exposure. Results of the current study establish a significant relationship between Cav1 and the activation of cell signaling pathways in response to nsPEFs.

Graphic Abstract



中文翻译:

Caveolin-1 参与调节细胞对纳秒脉冲电场的生物反应

摘要

纳秒脉冲电场 (nsPEF) 诱导质膜 (PM) 发生变化,包括 PM 透化(称为纳米穿孔),允许离子自由进入细胞,并在某些情况下导致细胞死亡。我们实验室最近的研究表明,PM 的组成是 PM 纳米穿孔的关键决定因素。因此,我们假设对 nsPEF 暴露的生物反应可能受到脂质微区的影响,包括小窝,这是 PM 的专门内陷,富含胆固醇并含有重要的细胞信号蛋白的聚集体,如小窝蛋白-1 (Cav1) . Caveolae 在细胞信号转导中发挥重要作用,包括通过 Cav1 与调节信号蛋白的相互作用来控制钙流入和细胞死亡。目前的结果表明,Cav1 的消耗增加了钙的流入,而 Cav1 过表达产生了相反的效果。此外,已知 Cav1 可以结合和隔离小窝内重要的细胞信号蛋白,从而使结合伙伴失活。nsPEF 暴露后 PM 的成像显示 PM Cav1 的局部消耗,共免疫沉淀研究的结果显示两个关键的 Cav1 结合伙伴(瞬时受体电位阳离子通道亚家族 C1(TRPC1 ) 和肌醇三磷酸受体 (IP 3 R)) 在暴露于 nsPEFs 后。从 Cav1释放 TRPC 1和 IP 3 R 将激活下游信号级联,包括储存操作的钙进入,这可以解释 nsPEF 暴露后钙的流入。当前研究的结果建立了 Cav1 与响应 nsPEF 的细胞信号通路激活之间的重要关系。

图形摘要

更新日期:2021-01-11
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