Abstract
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with the selective loss of motor neurons in the brain, brain stem, and spinal cord. A number of the mutants of the human gene for superoxide dismutase 1 (SOD1) have been shown to cause familial ALS as a result of gain-of-function toxicity by an unknown mechanism. In this study, we show that glyceraldehyde-3-phosphate dehydrogenase (GAPDH) functions as a critical mediator of the apoptotic cell death signaling cascade induced by the ALS-associated G93A mutant of human SOD1 [SOD1(G93A)]. We observed that SOD1(G93A) induces S-nitrosylation of GAPDH and the subsequent binding of GAPDH and Siah1 in NSC34 motor neuron-like cells. Furthermore, SOD1(G93A) promoted nuclear translocation of S-nitrosylated GAPDH in the cells. In addition, SOD1(G93A)-induced apoptotic cell death was inhibited by deprenyl, a chemical inhibitor of GAPDH S-nitrosylation, in NSC34 cells. Taken together, our findings suggest that S-nitrosylation of GAPDH plays a critical role in SOD1(G93A)-induced neuronal apoptosis.
Original language | English |
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Pages (from-to) | 310-316 |
Number of pages | 7 |
Journal | Animal Cells and Systems |
Volume | 20 |
Issue number | 6 |
DOIs | |
Publication status | Published - 2016 Nov 1 |
Keywords
- Amyotrophic lateral sclerosis
- GAPDH
- S-nitrosylation
- deprenyl
- superoxide dismutase 1 (G93A)
ASJC Scopus subject areas
- Animal Science and Zoology
- Biochemistry, Genetics and Molecular Biology(all)