Glyceraldehyde-3-phosphate dehydrogenase: Nuclear translocation participates in neuronal and nonneuronal cell death

Glyceraldehyde-3-phosphate dehydrogenase: Nuclear translocation participates in neuronal and nonneuronal cell death

Departments of Neuroscience, Pharmacology and Molecular Sciences, and Psychiatry, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205

Contributed by Solomon H. Snyder

Abstract

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) protein levels increase in particulate fractions in association with cell death in HEK293 cells, S49 cells, primary thymocytes, PC12 cells, and primary cerebral cortical neuronal cultures. Subcellular fractionation and immunocytochemistry reveal that this increase primarily reflects nuclear translocation. Nuclear GAPDH is tightly bound, resisting extraction by DNase or salt treatment. Treating primary thymocytes, PC12 cells, and primary cortical neurons with antisense but not sense oligonucleotides to GAPDH prevents cell death. Because cell-death-associated nuclear translocation of GAPDH and antisense protection occur in multiple neuronal and nonneuronal systems, we propose that GAPDH is a general mediator of cell death and uses nuclear translocation as a signaling mechanism.

Footnotes

ABBREVIATIONS:

Ab,

antibody;

Dex,

dexamethasone;

FBS,

fetal bovine serum;

GAPDH,

glyceraldehyde-3-phosphate dehydrogenase;

HD,

Huntington disease;

LDH,

lactate dehydrogenase;

NGF,

nerve growth factor;

PMSF,

phenylmethylsulfonyl fluoride;

HP,

high-speed pellet;

LP,

low-speed pellet