Priority Research Paper Volume 14, Issue 1 pp 4—27

AMP-activated protein kinase-dependent nuclear localization of glyceraldehyde 3-phosphate dehydrogenase in senescent human diploid fibroblasts

Jee Young Sohn1, *, , Hyeok-Jin Kwak2, *, , Ji Heon Rhim3, , Eui-Ju Yeo2,4, ,

  • 1 Department of Medicine, College of Medicine, Gachon University, Incheon 21999, Republic of Korea
  • 2 Department of Health Sciences and Technology, GAIHST, Gachon University, Incheon 21999, Republic of Korea
  • 3 Bio-New Material Development, NineBioPharm Co., Ltd., Cheongju 28161, Republic of Korea
  • 4 Department of Biochemistry, College of Medicine, Gachon University, Incheon 21999, Republic of Korea
* Equal contribution

Received: June 15, 2021       Accepted: January 3, 2022       Published: January 12, 2022
How to Cite

Copyright: © 2022 Sohn et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a key glycolytic enzyme that participates in various cellular events, such as DNA repair and apoptosis. The functional diversity of GAPDH depends on its intracellular localization. Because AMP-activated protein kinase (AMPK) regulates the nuclear translocation of GAPDH in young cells and AMPK activity significantly increases during aging, we investigated whether altered AMPK activity is involved in the nuclear localization of GAPDH in senescent cells. Age-dependent nuclear translocation of GAPDH was confirmed by confocal laser scanning microscopy in human diploid fibroblasts (HDFs) and by immunohistochemical analysis in aged rat skin cells. Senescence-induced nuclear localization was reversed by lysophosphatidic acid but not by platelet-derived growth factor. The extracellular matrix from young cells also induced the nuclear export of GAPDH in senescent HDFs. An activator of AMPK, 5-Aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR), increased the level of nuclear GAPDH, whereas an inhibitor of AMPK, Compound C, decreased the level of nuclear GAPDH in senescent HDFs. Transfection with AMPKα siRNA prevented nuclear translocation of GAPDH in senescent HDFs. The stimulatory effect of AICAR and serum depletion on GAPDH nuclear translocation was reduced in AMPKα1/α2-knockout mouse embryonic fibroblasts. Overall, increased AMPK activity may play a role in the senescence-associated nuclear translocation of GAPDH.


AICAR: 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside; AMPK: AMP-activated protein kinase; CompC: 6-[4-(2-Piperidin-1-yl-ethoxy)-phenyl]-3-pyridin-4-yl-pyrazolo [1,5-a] pyrimidine; ECM: extracellular matrix; FBS: fetal bovine serum; FITC: fluorescein isothiocyanate; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; HDF: human diploid fibroblast; LPA: lysophosphatidic acid; PDGF: platelet-derived growth factor; PI3K: phosphoinositide 3-kinase; SFM: serum free medium.