Effects of tissue transglutaminase on beta -amyloid1-42-induced apoptosis.
Tissue transglutaminase (TGase) has been implicated in both cell survival and apoptosis. Here we investigate the role of TGase in beta-amyloid-induced neurotoxicity using retinoic acid (RA)-differentiated, neuronal SH-SY5Y cells. We show that beta-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 beta-amyloid1-42-induced apoptosis, whereas transamidation-defective TGase did not. These effects were specific for beta-amyloid-treated cells, as TGase reversed the neurotoxic effects caused by hydrogen peroxide treatment. Enhancement of beta-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 beta-amyloid-induced recruitment of TGase to the cell surface accentuating neuronal toxicity and apoptosis.
Wakshlag
Joseph J
JJ
Department of Molecular Medicine, Cornell University, Ithaca, NY 14853, USA.
Antonyak
Marc A
MA
Boehm
Jason E
JE
Boehm
Karen
K
Cerione
Richard A
RA
D016229:Amyloid beta-Peptides / Q000378:metabolism* / Q000633:toxicity; D017209:Apoptosis; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D002470:Cell Survival; D019204:GTP-Binding Proteins / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism* / Q000633:toxicity; D014162:Transfection; D011503:Transglutaminases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D014212:Tretinoin / Q000494:pharmacology
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D014212:Tretinoin; D006861:Hydrogen Peroxide; D011503:Transglutaminases; D019204:GTP-Binding Proteins