TY - JOUR
T1 - Cold atmospheric plasma (CAP), a novel physicochemical source, induces neural differentiation through cross-talk between the specific RONS cascade and Trk/Ras/ERK signaling pathway
AU - Jang, Ja Young
AU - Hong, Young June
AU - Lim, Junsup
AU - Choi, Jin Sung
AU - Choi, Eun Ha
AU - Kang, Seongman
AU - Rhim, Hyangshuk
N1 - Funding Information:
This work was supported by the National Research Foundation of Korea (NRF) Grant funded by the Korean Government (MSIP: Ministry of Science, ICT and Future Planning) (NRF-2015M2B2A9031726), (NRF-2016R1A2B4009375), (NRF-2015R1A2A2A01003516), (HI17C0509) and (NRF-2016K1A4A3914113). We thank the Korea Zebrafish Organogenesis Mutant Bank (ZOMB) for providing zebrafish tg[elavl3:EGFP]knu3.
Publisher Copyright:
© 2017
PY - 2018/2
Y1 - 2018/2
N2 - Plasma, formed by ionization of gas molecules or atoms, is the most abundant form of matter and consists of highly reactive physicochemical species. In the physics and chemistry fields, plasma has been extensively studied; however, the exact action mechanisms of plasma on biological systems, including cells and humans, are not well known. Recent evidence suggests that cold atmospheric plasma (CAP), which refers to plasma used in the biomedical field, may regulate diverse cellular processes, including neural differentiation. However, the mechanism by which these physicochemical signals, elicited by reactive oxygen and nitrogen species (RONS), are transmitted to biological system remains elusive. In this study, we elucidated the physicochemical and biological (PCB) connection between the CAP cascade and Trk/Ras/ERK signaling pathway, which resulted in neural differentiation. Excited atomic oxygen in the plasma phase led to the formation of RONS in the PCB network, which then interacted with reactive atoms in the extracellular liquid phase to form nitric oxide (NO). Production of large amounts of superoxide radical ([rad]O2 −) in the mitochondria of cells exposed to CAP demonstrated that extracellular NO induced the reversible inhibition of mitochondrial complex IV. We also demonstrated that cytosolic hydrogen peroxide, formed by [rad]O2 − dismutation, act as an intracellular messenger to specifically activate the Trk/Ras/ERK signaling pathway. This study is the first to elucidate the mechanism linking physicochemical signals from the CAP cascade to the intracellular neural differentiation signaling pathway, providing physical, chemical and biological insights into the development of therapeutic techniques to treat neurological diseases.
AB - Plasma, formed by ionization of gas molecules or atoms, is the most abundant form of matter and consists of highly reactive physicochemical species. In the physics and chemistry fields, plasma has been extensively studied; however, the exact action mechanisms of plasma on biological systems, including cells and humans, are not well known. Recent evidence suggests that cold atmospheric plasma (CAP), which refers to plasma used in the biomedical field, may regulate diverse cellular processes, including neural differentiation. However, the mechanism by which these physicochemical signals, elicited by reactive oxygen and nitrogen species (RONS), are transmitted to biological system remains elusive. In this study, we elucidated the physicochemical and biological (PCB) connection between the CAP cascade and Trk/Ras/ERK signaling pathway, which resulted in neural differentiation. Excited atomic oxygen in the plasma phase led to the formation of RONS in the PCB network, which then interacted with reactive atoms in the extracellular liquid phase to form nitric oxide (NO). Production of large amounts of superoxide radical ([rad]O2 −) in the mitochondria of cells exposed to CAP demonstrated that extracellular NO induced the reversible inhibition of mitochondrial complex IV. We also demonstrated that cytosolic hydrogen peroxide, formed by [rad]O2 − dismutation, act as an intracellular messenger to specifically activate the Trk/Ras/ERK signaling pathway. This study is the first to elucidate the mechanism linking physicochemical signals from the CAP cascade to the intracellular neural differentiation signaling pathway, providing physical, chemical and biological insights into the development of therapeutic techniques to treat neurological diseases.
KW - Cold atmospheric plasma (CAP)
KW - Neural differentiation
KW - Neurological disease
KW - Plasma
KW - Reactive oxygen and nitrogen species (RONS)
UR - http://www.scopus.com/inward/record.url?scp=85037523802&partnerID=8YFLogxK
U2 - 10.1016/j.biomaterials.2017.11.045
DO - 10.1016/j.biomaterials.2017.11.045
M3 - Article
C2 - 29222974
AN - SCOPUS:85037523802
VL - 156
SP - 258
EP - 273
JO - Biomaterials
JF - Biomaterials
SN - 0142-9612
ER -