Induction of Cell Death Mechanisms and Apoptosis by Nanosecond Pulsed Electric Fields (nsPEFs)

Cells

Stephen J. Beebe¹  Nova M. Sain¹ 

[1] Frank Reidy Research Center for Bioelectrics, Old Dominion University, 4211 Monarch Way, IRP2, Norfolk, Virginia, 23508, USA; E-Mail:

关键词: apoptosis;    caspase-dependent;    caspase-independent;    Jurkat clones;    APAF-1;    FADD;    N1-S1 hepatocellular carcinoma cells;    Ca²⁺ mobilization;    mitochondria membrane potential;    mitochondria permeability transition pore;    cytochrome c;    electroporation;    nanopores 3-10.;   

DOI  :  10.3390/cells2010136

来源: mdpi

【 摘 要 】

Pulse power technology using nanosecond pulsed electric fields (nsPEFs) offers a new stimulus to modulate cell functions or induce cell death for cancer cell ablation. New data and a literature review demonstrate fundamental and basic cellular mechanisms when nsPEFs interact with cellular targets. NsPEFs supra-electroporate cells creating large numbers of nanopores in all cell membranes. While nsPEFs have multiple cellular targets, these studies show that nsPEF-induced dissipation of ΔΨm closely parallels deterioration in cell viability. Increases in intracellular Ca²⁺ alone were not sufficient for cell death; however, cell death depended of the presence of Ca²⁺. When both events occur, cell death ensues. Further, direct evidence supports the hypothesis that pulse rise-fall times or high frequency components of nsPEFs are important for decreasing ΔΨm and cell viability. Evidence indicates in Jurkat cells that cytochrome c release from mitochondria is caspase-independent indicating an absence of extrinsic apoptosis and that cell death can be caspase-dependent and –independent. The Ca²⁺ dependence of nsPEF-induced dissipation of ΔΨm suggests that nanoporation of inner mitochondria membranes is less likely and effects on a Ca²⁺-dependent protein(s) or the membrane in which it is embedded are more likely a target for nsPEF-induced cell death. The mitochondria permeability transition pore (mPTP) complex is a likely candidate. Data demonstrate that nsPEFs can bypass cancer mutations that evade apoptosis through mechanisms at either the DISC or the apoptosome.

【 授权许可】

CC BY   
© 2013 by the authors; licensee MDPI, Basel, Switzerland.