Related Experiment Video

Updated: Oct 4, 2026

Development of an Insert Co-culture System of Two Cellular Types in the Absence of Cell-Cell Contact
11:29

Development of an Insert Co-culture System of Two Cellular Types in the Absence of Cell-Cell Contact

Published on: July 17, 2016

Induction of CHOP and apoptosis by nitric oxide in p53-deficient microglial cells

K Kawahara1, S Oyadomari, T Gotoh

  • 1Department of Molecular Genetics, Kumamoto University School of Medicine, Honjo, Japan.

FEBS Letters
|October 10, 2001
PubMed

Insights

Excessive nitric oxide (NO) causes neurotoxicity via endoplasmic reticulum (ER) stress and CHOP induction, independent of the p53 pathway. This finding reveals a novel mechanism in NO-induced cell death.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Molecular Biology

Background:

  • Excessive nitric oxide (NO) is linked to neurotoxicity following ischemic events.
  • Current understanding suggests NO toxicity involves DNA damage-p53 or mitochondrial pathways.
  • The precise molecular mechanisms underlying NO-induced neurotoxicity require further elucidation.

Purpose of the Study:

  • To investigate the specific mechanism of nitric oxide (NO) toxicity in neuronal cells.
  • To determine the role of the p53 pathway and endoplasmic reticulum (ER) stress in NO-induced apoptosis.
  • To utilize p53-deficient murine microglial cells for mechanistic studies.

Main Methods:

  • Utilized p53-deficient murine microglial MG5 cells.
  • Stimulated cells with bacterial lipopolysaccharide (LPS) and interferon-gamma (IFN-γ).
  • Assessed mRNA and protein expression of inducible NO synthase (iNOS), CHOP/GADD153, and ER chaperone Bip/GRP78.
  • Administered NO donors (SNAP, NOC18) and a peroxynitrite generator (SIN-1) to evaluate NO-specific effects.

Main Results:

  • LPS plus IFN-γ induced iNOS and apoptosis in MG5 cells.
  • CHOP/GADD153, an ER stress-related transcription factor, was upregulated following NO induction.
  • NO donors and peroxynitrite generators induced both CHOP/GADD153 and the ER chaperone Bip/GRP78.
  • CHOP mRNA induction exhibited a time lag relative to iNOS mRNA induction.

Conclusions:

  • Nitric oxide (NO) induces apoptosis in microglial cells through the endoplasmic reticulum (ER) stress pathway involving CHOP/GADD153.
  • This NO-induced apoptotic pathway is independent of the p53 tumor suppressor protein.
  • The findings highlight ER stress as a critical mediator of NO-induced neurotoxicity.

More Related Videos

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death09:18

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death

Published on: December 27, 2016

Related Concept Videos

The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
Phagocytosis of Apoptotic Cells01:17

Phagocytosis of Apoptotic Cells

Cells undergoing apoptosis form apoptotic bodies that must be removed immediately to prevent inflammation, autoimmune diseases, and necrosis. Phagocytosis is carried out by professional phagocytes such as macrophages or  immature dendritic cells. Non-professional phagocytes such as  epithelial cells and fibroblasts also take part in this process; however, they are not as effective as professional phagocytes. 
Normal cells contain receptors that prevent them from being recognized by phagocytes.
The Extrinsic Apoptotic Pathway01:17

The Extrinsic Apoptotic Pathway

The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
Apoptosis01:30

Apoptosis

Apoptosis is a combination of two Greek words, 'apo' and 'ptosis,' meaning separation and falling off, respectively. Hippocrates used this word to describe gangrene, which was caused due to bandaging of fractured bones. Apoptosis was distinguished from necrosis in 1970 when John Kerr reported observations of morphological changes occurring during apoptosis. During one experiment, he observed that the disruption of blood supply to the liver tissue resulted in a size reduction of the tissue.