Adult human dermal fibroblasts exposed to nanosecond electrical pulses exhibit genetic biomarkers of mechanical stress

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, s...

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Main Authors: Caleb C. Roth, Randolph D. Glickman, Stacey L. Martens, Ibtissam Echchgadda, Hope T. Beier, Ronald A. Barnes, Jr., Bennett L. Ibey
Format: Article
Language:English
Published: Elsevier 2017-03-01
Series:Biochemistry and Biophysics Reports
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2405580817300304
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author Caleb C. Roth
Randolph D. Glickman
Stacey L. Martens
Ibtissam Echchgadda
Hope T. Beier
Ronald A. Barnes, Jr.
Bennett L. Ibey
author_facet Caleb C. Roth
Randolph D. Glickman
Stacey L. Martens
Ibtissam Echchgadda
Hope T. Beier
Ronald A. Barnes, Jr.
Bennett L. Ibey
author_sort Caleb C. Roth
collection DOAJ
description 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.
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spelling doaj.art-eff04149c7dd45189142633273613c302022-12-21T18:42:18ZengElsevierBiochemistry and Biophysics Reports2405-58082017-03-019C30230910.1016/j.bbrep.2017.01.007Adult human dermal fibroblasts exposed to nanosecond electrical pulses exhibit genetic biomarkers of mechanical stressCaleb C. Roth0Randolph D. Glickman1Stacey L. Martens2Ibtissam Echchgadda3Hope T. Beier4Ronald A. Barnes, Jr.5Bennett L. Ibey6University of Texas Health Science Center San Antonio, School of Medicine, Dept. of Radiological Sciences, 7703 Floyd Curl Drive, San Antonio, TX 78229, USAUniversity of Texas Health Science Center San Antonio, School of Medicine, Dept. of Ophthalmology, 7703 Floyd Curl Drive, San Antonio, TX 78229, USAHuman Effectiveness Directorate, 711th Human Performance Wing, Air Force Research Laboratory, Radio Frequency Bioeffects Branch, Bioeffects Division, 4141 Petroleum Road, JBSA Fort Sam Houston, TX 78234, USAHuman Effectiveness Directorate, 711th Human Performance Wing, Air Force Research Laboratory, Radio Frequency Bioeffects Branch, Bioeffects Division, 4141 Petroleum Road, JBSA Fort Sam Houston, TX 78234, USAHuman Effectiveness Directorate, 711th Human Performance Wing, Air Force Research Laboratory, Optical Radiation Bioeffects Branch, Bioeffects Division, 4141 Petroleum Road, JBSA Fort Sam Houston, TX 78234, USAHuman Effectiveness Directorate, 711th Human Performance Wing, Air Force Research Laboratory, Radio Frequency Bioeffects Branch, Bioeffects Division, 4141 Petroleum Road, JBSA Fort Sam Houston, TX 78234, USAHuman Effectiveness Directorate, 711th Human Performance Wing, Air Force Research Laboratory, Radio Frequency Bioeffects Branch, Bioeffects Division, 4141 Petroleum Road, JBSA Fort Sam Houston, TX 78234, USABackground: 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.http://www.sciencedirect.com/science/article/pii/S2405580817300304Adult human dermal fibroblastsMechanical stressMicroarrayNanosecond electrical pulseFOSITPKB
spellingShingle Caleb C. Roth
Randolph D. Glickman
Stacey L. Martens
Ibtissam Echchgadda
Hope T. Beier
Ronald A. Barnes, Jr.
Bennett L. Ibey
Adult human dermal fibroblasts exposed to nanosecond electrical pulses exhibit genetic biomarkers of mechanical stress
Biochemistry and Biophysics Reports
Adult human dermal fibroblasts
Mechanical stress
Microarray
Nanosecond electrical pulse
FOS
ITPKB
title Adult human dermal fibroblasts exposed to nanosecond electrical pulses exhibit genetic biomarkers of mechanical stress
title_full Adult human dermal fibroblasts exposed to nanosecond electrical pulses exhibit genetic biomarkers of mechanical stress
title_fullStr Adult human dermal fibroblasts exposed to nanosecond electrical pulses exhibit genetic biomarkers of mechanical stress
title_full_unstemmed Adult human dermal fibroblasts exposed to nanosecond electrical pulses exhibit genetic biomarkers of mechanical stress
title_short Adult human dermal fibroblasts exposed to nanosecond electrical pulses exhibit genetic biomarkers of mechanical stress
title_sort adult human dermal fibroblasts exposed to nanosecond electrical pulses exhibit genetic biomarkers of mechanical stress
topic Adult human dermal fibroblasts
Mechanical stress
Microarray
Nanosecond electrical pulse
FOS
ITPKB
url http://www.sciencedirect.com/science/article/pii/S2405580817300304
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