Sun G, Wang X, Li T, Qu S, Sun J
1 The First Affiliated Hospital of Dalian Medical University, Liaoning, China.
2 Institute of Cancer Stem Cell, Dalian Medical University, Dalian, Liaoning, China.
Hum Exp Toxicol. 2018 Jan 1:960327118765335. doi: 10.1177/0960327118765335.
As a potent neurotoxic agent, acrylamide (ACR) is formed in food processing at higher temperature. Taurine (TAU), a nonessential amino acid, is used to cure neurodegenerative disorders, followed by activation of the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathway. In this article, we certified that antiapoptotic efficacy of TAU in vivo and vitro. ACR-treated rats received TAU by drinking water 2 weeks after ACR intoxication. The results showed that in treated rats, TAU alleviated ACR-induced neuronal apoptosis, which was associated with the activation of PI3K/AKT signaling pathway. TAU attenuated apoptosis caused by ACR through observing terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)-positive cells, measure of protein expression of Bcl-2, Bax, and caspase 3 activity. TAU-induced antiapoptotic effect is PI3K/AKT-dependent, which was proved in ACR-intoxicated ventral spinal cord 4.1 cells in the presence of AKT inhibitor, MK-2206. Therefore, our results demonstrated that TAU-attenuated ACR-induced apoptosis in vivo through a PI3K/AKT-dependent manner provided new sights in the molecular mechanism of TAU protection against ACR-induced neurotoxicity.
作为一种强效神经毒剂，丙烯酰胺（ACR）在高温食品加工过程中形成。牛磺酸（TAU）是一种非必需氨基酸，用于治疗神经退行性疾病，随后激活磷脂酰肌醇3激酶/蛋白激酶B（PI3K/AKT）信号通路。在本文中，我们证实了TAU在体内和体外的抗凋亡功效。ACR处理的大鼠在ACR中毒2周后通过饮水给予TAU。结果表明，在处理的大鼠中，TAU减轻了ACR诱导的神经元凋亡，这与PI3K/AKT信号通路的激活有关。TAU通过观察末端脱氧核苷酸转移酶介导的dUTP缺口末端标记（TUNEL）阳性细胞、测量Bcl-2、Bax的蛋白表达和caspase 3活性，减轻了ACR引起的凋亡。在存在AKT抑制剂MK-2206的情况下，在ACR中毒的腹侧脊髓4.1细胞中证明，TAU诱导的抗凋亡作用是PI3K/AKT依赖性的。因此，我们的结果表明，TAU通过PI3K/AKT依赖性方式减轻体内ACR诱导的凋亡，为TAU保护免受ACR诱导的神经毒性的分子机制提供了新的见解。
