TY - JOUR
T1 - Adult human dermal fibroblasts exposed to nanosecond electrical pulses exhibit genetic biomarkers of mechanical stress
AU - Roth, Caleb C.
AU - Glickman, Randolph D.
AU - Martens, Stacey L.
AU - Echchgadda, Ibtissam
AU - Beier, Hope T.
AU - Barnes, Ronald A.
AU - Ibey, Bennett L.
N1 - Funding Information:
We wish to thank the SMART Program (Grant no. N002440910081) Office of Secretary Defense-Test and Evaluation, Defense-Wide / PE0601120D8Z National Defense Education Program / BA-1, Basic Research and the Air Force Research Laboratory for providing us with the opportunity to conduct this study. This study was also supported by a grant from the Air Force Office of Scientific Research (Grant no. LRIR 16RHCOR348).
Publisher Copyright:
© 2017
PY - 2017/3/1
Y1 - 2017/3/1
N2 - 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.
AB - 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.
KW - Adult human dermal fibroblasts
KW - FOS
KW - ITPKB
KW - Mechanical stress
KW - Microarray
KW - Nanosecond electrical pulse
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U2 - 10.1016/j.bbrep.2017.01.007
DO - 10.1016/j.bbrep.2017.01.007
M3 - Article
AN - SCOPUS:85011357000
VL - 9
SP - 302
EP - 309
JO - Biochemistry and Biophysics Reports
JF - Biochemistry and Biophysics Reports
SN - 2405-5808
ER -