Related Experiment Video

Updated: Jun 13, 2026

Application of Genetically Encoded Fluorescent Nitric Oxide (NO•) Probes, the geNOps, for Real-time Imaging of NO• Signals in Single Cells
08:32

Application of Genetically Encoded Fluorescent Nitric Oxide (NO•) Probes, the geNOps, for Real-time Imaging of NO• Signals in Single Cells

Published on: March 16, 2017

Nitric oxide induction of IRE1-alpha-dependent CREB phosphorylation in human glioma cells

Yeon Hyang Kim1, Han Seung Joo, Doo-Sik Kim

  • 1Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, Republic of Korea. yeonhkim@yonsei.ac.kr

Nitric Oxide : Biology and Chemistry
|May 8, 2010
PubMed

Insights

Nitric oxide (NO) triggers endoplasmic reticulum (ER) stress and cell death in glioma cells by activating the IRE1-alpha/TRAF2/JNK pathway. This NO-induced pathway leads to CREB phosphorylation, contributing to glioma cell death.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Neuro-oncology

Background:

  • Endoplasmic reticulum (ER) stress is implicated in various cell death pathways.
  • Nitric oxide (NO) plays diverse roles in cellular signaling and physiology.
  • Glioma is a primary brain tumor with significant unmet therapeutic needs.

Purpose of the Study:

  • To investigate the role of nitric oxide (NO) in ER-related cell death in human glioma cells.
  • To elucidate the molecular mechanisms by which NO influences ER stress and cell viability.
  • To identify potential therapeutic targets within the NO-mediated signaling cascade.

Main Methods:

  • Human glioma cell lines (CRT-MG, U87MG) and normal astrocytes were used.
  • Cells were treated with NO donors (SNAP) and ER stress inducers (thapsigargin).
  • Molecular analyses included Western blotting, siRNA knockdown, and assessment of calcium levels and apoptosis.

Main Results:

  • NO donors and ER stress inducers increased cytosolic Ca(2+) and apoptosis in glioma cells.
  • NO activated the ER-associated IRE1-alpha/TRAF2/JNK pathway, leading to CREB phosphorylation.
  • Upregulation of IRE1-alpha and phospho-CREB was observed in glioma cells compared to astrocytes.
  • Interleukin-1beta also induced NO-associated cell death, increasing IRE1-alpha and p-CREB levels.

Conclusions:

  • Intracellular NO modulates the IRE1-alpha-dependent CREB phosphorylation pathway in human glioma cells.
  • The IRE1-alpha-dependent phospho-CREB signaling pathway, responsive to NO/Ca(2+), is crucial for ER-related cell death in glioma.
  • Targeting this pathway may offer a novel therapeutic strategy for glioma treatment.

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