title: The role of tissue transglutaminase in 1-methyl-4-phenylpyridinium (MPP+)-induced toxicity in differentiated human SH-SY5Y neuroblastoma cells.
abstract: 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.
authors.affiliation: School of Biomedical and Natural Sciences, Nottingham Trent University, Clifton Lane, Nottingham NG11 8NS, UK.
authors.forename: Katy E
authors.initials: KE
authors.lastname: Beck
authors.forename: Luigi A
authors.initials: LA
authors.lastname: De Girolamo
authors.forename: Martin
authors.initials: M
authors.lastname: Griffin
authors.forename: E Ellen
authors.initials: EE
authors.lastname: Billett
mesh_terms: 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*
chemical_list: 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