The Protein Journal

, Volume 25, Issue 1, pp 83–94

Effects of Tissue Transglutaminase on β -Amyloid1-42-Induced Apoptosis

Authors

  • Joseph J. Wakshlag
    • Department of Molecular MedicineCornell University
  • Marc A. Antonyak
    • Department of Molecular MedicineCornell University
  • Jason E. Boehm
    • Department of Molecular MedicineCornell University
  • Karen Boehm
    • Molecular Biology/Genetic EngineeringNathan S. Kline Institute for Psychiatric Research
    • Department of Molecular MedicineCornell University
    • Department of Chemistry and Chemical BiologyCornell University
Article

DOI: 10.1007/s10930-006-0009-1

Cite this article as:
Wakshlag, J.J., Antonyak, M.A., Boehm, J.E. et al. Protein J (2006) 25: 83. doi:10.1007/s10930-006-0009-1

Tissue transglutaminase (TGase) has been implicated in both cell survival and apoptosis. Here we investigate the role of TGase in β-amyloid-induced neurotoxicity using retinoic acid (RA)-differentiated, neuronal SH-SY5Y cells. We show that β-amyloid-induced cell death was reduced in RA-differentiated SH-SY5Y cells treated with the TGase inhibitor monodansyl cadaverine. Expression of wild-type TGase enhanced β-amyloid1-42-induced apoptosis, whereas transamidation-defective TGase did not. These effects were specific for β-amyloid-treated cells, as TGase reversed the neurotoxic effects caused by hydrogen peroxide treatment. Enhancement of β-amyloid1-42-induced cell death by TGase was accompanied by marked increases in TGase activity in the membrane fractions and translocation of TGase to the cell surface. Overall, these findings suggest that the ability of TGase to exhibit pro-survival versus pro-apoptotic activity is linked to its cellular localization, with β-amyloid-induced recruitment of TGase to the cell surface accentuating neuronal toxicity and apoptosis.

Keywords

Alzheimer’s diseaseβ-amyloidapoptosisretinoic acidtransglutaminase

Abbreviations

GTP

guanosine triphosphate

MDC

monodansyl cadaverine

MTT

3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide

RA

all-trans-retinoic acid

Rb

retinoblastoma

TGase

tissue transglutaminase II.

Copyright information

© Springer Science+Business Media, Inc. 2006