PUBLICATION

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

Authors
Jang, J.Y., Hong, Y.J., Lim, J., Choi, J.S., Choi, E.H., Kang, S., Rhim, H.
ID
ZDB-PUB-180804-6
Date
2018
Source
Biomaterials   156: 258-273 (Journal)
Registered Authors
Keywords
Cold atmospheric plasma (CAP), Neural differentiation, Neurological disease, Plasma, Reactive oxygen and nitrogen species (RONS)
MeSH Terms
  • Animals
  • Catecholamines/metabolism
  • Cell Differentiation/drug effects*
  • Cell Line, Tumor
  • Cytosol/metabolism
  • Hydrogen Peroxide/metabolism
  • MAP Kinase Signaling System/drug effects*
  • Mice
  • Mitochondria/drug effects
  • Mitochondria/metabolism
  • Neural Stem Cells/cytology
  • Neural Stem Cells/drug effects
  • Neural Stem Cells/metabolism
  • Neurons/cytology*
  • Neurons/drug effects
  • Neurons/ultrastructure
  • Nitric Oxide/metabolism
  • Plasma Gases/pharmacology*
  • Reactive Nitrogen Species/metabolism*
  • Receptors, Nerve Growth Factor/metabolism*
  • Zebrafish
  • ras Proteins/metabolism*
PubMed
29222974 Full text @ Biomaterials
Abstract
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 (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 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.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping