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Related Concept Videos

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MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
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Nanosecond pulsed electric fields activate MAPK pathways in human cells.

Keiko Morotomi-Yano1, Hidenori Akiyama, Ken-ichi Yano

  • 1Bioelectrics Research Center, Kumamoto University, Kurokami, Kumamoto, Japan.

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Area of Science:

  • Cell Biology
  • Biophysics
  • Molecular Oncology

Background:

  • Nanosecond pulsed electric fields (nsPEFs) are explored for cancer therapy.
  • The precise molecular mechanisms underlying nsPEF effects on cells remain unclear.

Purpose of the Study:

  • To investigate the molecular pathways activated by nsPEFs in human cells.
  • To elucidate the role of mitogen-activated protein kinases (MAPKs) in nsPEF action.

Main Methods:

  • Exposure of HeLa S3 cells to nsPEFs.
  • Analysis of protein phosphorylation (MAPKs, downstream targets) using Western blotting.
  • Assessment of immediate early gene expression via transcription assays.
  • Pharmacological inhibition of MAPK pathways.

Main Results:

  • nsPEFs induced phosphorylation of key MAPKs (p38, JNK, ERK) and their upstream kinases.
  • Downstream targets like MSK1, Hsp27, ATF2, p90RSK, and c-Jun showed increased phosphorylation.
  • Transcriptional activation of immediate early genes within MAPK pathways was observed.
  • MAPK pathway inhibitors blocked nsPEF-induced downstream phosphorylation and gene expression.

Conclusions:

  • nsPEFs transiently activate MAPK signaling pathways in human cells.
  • This activation is functionally linked to downstream protein phosphorylation and gene expression changes.
  • nsPEFs present a novel tool for modulating biological phenomena via MAPK pathway control.