Homocysteine-induced toxicity increases TG2 expression in Neuro2a cells.
High levels of homocysteine promote cell damage mainly through induction of oxidative stress, endoplasmic reticulum (ER) stress, and activation of pro-inflammatory factors. The effects of homocysteine were here examined in the continuously dividing neuroblastoma cell line Neuro2a. Cell treatment with homocysteine (100-500 microM) for 4 h increased ROS production while reducing cell viability in a dose-dependent manner. Cell exposure to 250 microM homocysteine was able to induce transglutaminase 2 up-regulation and increased in situ transglutaminase activity. These effects were prevented by the incubation with the transglutaminase activity inhibitor cystamine. Homocysteine also induced NF-kappaB activation that seemed associated with transglutaminase 2 up-regulation since the specific NF-kappaB inhibition by SN50 was able to reduce transglutaminase expression and activity levels. In the light of these observations, it may be postulated that TG2 up-regulation is involved in cell response to homocysteine-induced stress, in which NF-kappaB activation plays also a pivotal role.
Currò
M
M
Department of Biochemical, Physiological and Nutritional Sciences, University of Messina, Policlinico Universitario, Via Consolare Valeria, 98125, Messina, Italy.
Condello
S
S
Caccamo
D
D
Ferlazzo
N
N
Parisi
G
G
Ientile
R
R
D000818:Animals; D015153:Blotting, Western; D002470:Cell Survival / Q000187:drug effects; D003538:Cystamine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D019204:GTP-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D006710:Homocysteine / Q000037:antagonists & inhibitors / Q000633:toxicity*; D007527:Isoenzymes / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000187:drug effects / Q000378:metabolism; D010084:Oxidation-Reduction; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D017382:Reactive Oxygen Species / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D011503:Transglutaminases / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured
D007527:Isoenzymes; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D006710:Homocysteine; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins; D003538:Cystamine