|
KMID : 1161520160200060310
|
|
Animal Cells and Systems
2016 Volume.20 No. 6 p.310 ~ p.316
|
|
|
S-nitrosylated GAPDH mediates neuronal apoptosis induced by amyotrophic lateral sclerosis-associated mutant SOD1G93A
|
|
Lee Ra-Na
Lim Jane Melissa
Roh Kyung-Hye
Kim Ji-Hyun
Kang Seong-Man
Lee Ji-Eun
Choi Eui-Ju
|
|
|
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.
|
|
|
KEYWORD
|
|
|
Amyotrophic lateral sclerosis, deprenyl, GAPDH, S-nitrosylation, superoxide dismutase 1 (G93A)
|
|
|
FullTexts / Linksout information
|
|
|
|
|
|
Listed journal information
|
|
 
|