S-nitrosylated GAPDH mediates neuronal apoptosis induced by amyotrophic lateral sclerosis-associated mutant SOD1G93A

Rana Lee, Jane Melissa Lim, Kyung Hye Roh, Ji Hyun Kim, Seongman Kang, Ji Eun Lee, Eui Ju Choi

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3 Citations (Scopus)


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 languageEnglish
Pages (from-to)310-316
Number of pages7
JournalAnimal Cells and Systems
Issue number6
Publication statusPublished - 2016 Nov 1

Bibliographical note

Funding Information:
This work was supported by the BRL grant [NRF 2015041919] funded by the Ministry of Science, ICT & Future Planning of Korea, by a Korea University grant [E.-J.C.], and by the National Research Foundation (NRF) grant [2016R1C1B2008930] funded by the Korean government (MSIP) (J.E.L.).

Publisher Copyright:
© 2016 Korean Society for Integrative Biology.


  • Amyotrophic lateral sclerosis
  • S-nitrosylation
  • deprenyl
  • superoxide dismutase 1 (G93A)

ASJC Scopus subject areas

  • Animal Science and Zoology
  • General Biochemistry,Genetics and Molecular Biology


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