title: Activation of autophagy in response to nanosecond pulsed electric field exposure.
abstract: Previous work demonstrated significant changes in cellular membranes following exposure of cells to nanosecond pulsed electric fields (nsPEF), including nanoporation and increases in intracellular calcium concentration. While it is known that nsPEF exposure can cause cell death, how cells repair and survive nsPEF-induced cellular damage is not well understood. In this paper, we investigated whether autophagy is stimulated following nsPEF exposure to repair damaged membranes, proteins, and/or organelles in a pro-survival response. We hypothesized that autophagy is activated to repair nsPEF-induced plasma membrane damage and overwhelming this compensatory mechanism results in cell death. Activation of autophagy and subsequent cell death pathways were assessed measuring toxicity, gene and protein expression of autophagy markers, and by monitoring autophagosome formation and maturation using fluorescent microscopy. Results show that autophagy is activated at subtoxic nsPEF doses, as a compensatory mechanism to repair membrane damage. However, prolonged exposure results in increased cell death and a concomitant decrease in autophagic markers. These results suggest that cells take an active role in membrane repair, through autophagy, following exposure to nsPEF.
authors: General Dynamics Information Technology, JBSA Fort Sam Houston, TX, USA. Electronic address: jody.ullery.ctr@us.af.mil.
authors: Jody C
authors: JC
authors: Ullery
authors: General Dynamics Information Technology, JBSA Fort Sam Houston, TX, USA.
authors: Melissa
authors: M
authors: Tarango
authors: School of Medicine, Department of Radiological Sciences, University of Texas Health Science Center San Antonio, San Antonio, TX 78229, USA.
authors: Caleb C
authors: CC
authors: Roth
authors: Air Force Research Laboratory, 711th Human Performance Wing, Human Effectiveness Directorate, Bioeffects Division, Radio Frequency Bioeffects Branch, JBSA Fort Sam Houston, TX, USA.
authors: Bennett L
authors: BL
authors: Ibey
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology* / Q000528:radiation effects*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D001343:Autophagy / Q000502:physiology* / Q000528:radiation effects*; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D011829:Radiation Dosage
chemical_list: D051017:Apoptosis Regulatory Proteins
keywords: Autophagy; CHO; Nanosecond electric pulse