Homocysteine-induced toxicity increases TG2 expression in Neuro2a cells

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• 作者：M. Curr¨° ; S. Condello ; D. Caccamo ; N. Ferlazzo ; G. Parisi and R. Ientile
• 关键词：Homocysteine ; Transglutaminases ; NF ; κ ; B ; Neuro2a cells ; ROS
• 刊名：Amino Acids
• 出版年：2009
• 出版时间：April, 2009
• 年：2009
• 卷：36
• 期：4
• 页码：725-730
• 全文大小：257.5 KB

文摘

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 μM) for 4 h increased ROS production while reducing cell viability in a dose-dependent manner. Cell exposure to 250 μM 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-κB activation that seemed associated with transglutaminase 2 up-regulation since the specific NF-κB 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-κB activation plays also a pivotal role.