Related Experiment Video
Updated: Aug 9, 2026
10:36
Measurements of Physiological Stress Responses in C. Elegans
Published on: May 21, 2020
GAPDH as a sensor of NO stress
Makoto R Hara1, Matthew B Cascio, Akira Sawa
1Department of Neuroscience, Johns Hopkins University School of Medicine, 600 North Wolfe street, Baltimore, MD 21287, USA.
Biochimica Et Biophysica Acta
|April 1, 2006
Summary
Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) acts as a cell death mediator. Nitric oxide modifies GAPDH, leading to nuclear translocation and cytotoxicity, potentially linking it to neurodegenerative diseases.
Area of Science:
- Biochemistry
- Cell Biology
- Neuroscience
Background:
- Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a key glycolytic enzyme with emerging roles beyond metabolism.
- Evidence indicates GAPDH mediates cell death, particularly under oxidative stress conditions.
- Nuclear translocation of GAPDH is observed in response to various cellular stressors.
Purpose of the Study:
- To elucidate the molecular mechanisms of GAPDH-mediated cell death.
- To explore the role of the NO/GAPDH/Siah1 pathway in neurodegenerative disorders.
- To investigate the potential therapeutic implications of targeting the NO/GAPDH/Siah1 cascade.
Main Methods:
- Investigated the S-nitrosylation of GAPDH at C150 by nitric oxide (NO).
- Examined the interaction between modified GAPDH and Siah1, an E3 ubiquitin ligase.
- Studied the nuclear translocation of the GAPDH-Siah1 complex and its effect on Siah1 substrates.
Main Results:
- S-nitrosylation of GAPDH by NO facilitates its binding to Siah1.
- The GAPDH-Siah1 complex translocates to the nucleus, leading to the degradation of Siah1 substrates.
- This cascade results in cytotoxicity and is implicated in neurodegenerative processes like Alzheimer's disease.
Conclusions:
- The NO/GAPDH/Siah1 pathway is a critical mediator of cell death.
- Understanding this pathway offers insights into neurodegenerative disorders.
- Targeting the NO/GAPDH/Siah1 cascade presents potential therapeutic strategies for neuroprotection.
