The role of tissue transglutaminase in 1-methyl-4-phenylpyridinium (MPP+)-induced toxicity in differentiated human SH-SY5Y neuroblastoma cells.
Tissue transglutaminase (TG2) can induce post-translational modification of proteins, resulting in protein cross-linking or incorporation of polyamines into substrates, and can also function as a signal transducing G protein. The role of TG2 in the formation of insoluble cross-links has led to its implication in some neurodegenerative conditions. Exposure of pre-differentiated SH-SY5Y cells to the Parkinsonian neurotoxin 1-methyl-4-phenylpyridinium ion (MPP(+)) resulted in significant dose-dependent reductions in TG2 protein levels, measured by probing Western blots with a TG2-specific antibody. Transglutaminase (TG) transamidating activity, on the other hand, monitored by incorporation of a polyamine pseudo-substrate into cellular proteins, was increased. Inhibitors of TG (putrescine) and TG2 (R283) exacerbated MPP(+) toxicity, suggesting that activation of TG2 may promote a survival response in this toxicity paradigm.
Beck
Katy E
KE
School of Biomedical and Natural Sciences, Nottingham Trent University, Clifton Lane, Nottingham NG11 8NS, UK.
De Girolamo
Luigi A
LA
Griffin
Martin
M
Billett
E Ellen
EE
D015655:1-Methyl-4-phenylpyridinium / Q000633:toxicity*; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D019204:GTP-Binding Proteins; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D009447:Neuroblastoma; D010300:Parkinson Disease / Q000201:enzymology; D011073:Polyamines / Q000378:metabolism; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011700:Putrescine / Q000494:pharmacology; D011503:Transglutaminases / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*
D007093:Imidazoles; D011073:Polyamines; C088947:1,3-dimethyl-2-((2-oxopropyl)thio)imidazolium; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins; D015655:1-Methyl-4-phenylpyridinium; D011700:Putrescine