Regulation of taurine in OTA-induced apoptosis and autophagy
Regulation of taurine in OTA-induced apoptosis and autophagy
复制标题
DOI：
10.1016/j.toxicon.2020.04.097
复制
发表时间：
2020-07-15
期刊：
影响因子：
2.8
通讯作者：
Chen, Xingxiang
中科院分区：
文献类型：
--
作者：
Liu, Kai;Mao, Xinru;Chen, Xingxiang
赭曲霉毒素A（OTA）是一种毒性最强的真菌毒素，对动物和人体具有多种毒性作用，尤其是肾毒性。牛磺酸是一种广泛分布的细胞保护性氨基酸，是维持细胞完整性和稳态的基本因素。然而，牛磺酸在OTA诱导的肾毒性中的潜在作用仍然未知。在本研究中，我们证明，OTA处理在4.0-8.0 μ M增加PK-15细胞的凋亡，如通过增加凋亡和Bax和切割的caspase-3的蛋白表达的比率，减少Bcl-2的蛋白表达所示。同时，OTA处理引发自噬，如通过显著增加LC 3-II的蛋白表达和GFP-LC 3点的荧光强度所示。补充牛磺酸可降低OTA诱导的细胞毒性，并减弱细胞凋亡，如Annexin V/PI染色减少和凋亡相关蛋白（包括Bax和caspase-3）表达减少所示。同时，牛磺酸通过降低LC 3-II的蛋白表达和GFP-LC 3点的荧光强度来抑制OTA诱导的自噬，维持细胞内环境的稳定。结论牛磺酸可减轻OTA诱导的PK-15细胞凋亡，抑制其引发的自噬。我们的研究为牛磺酸在减少OTA诱导的肾毒性中的潜在作用提供了支持性数据。
Ochratoxin A (OTA), one of the most deleterious mycotoxins, could cause a variety of toxicological effects especially nephrotoxicity in animals and humans. Taurine, a wide-distributed cytoprotective amino acid, plays an important role as a basic factor for maintaining cellular integrity homeostasis. However, the potential effect of taurine in OTA-induced nephrotoxicity remains unknown. In the present study, we demonstrated that OTA treatment at 4.0-8.0 mu M increased apoptosis in PK-15 cells as shown by increased the ratio of apoptosis and protein expression of Bax and cleaved-caspase-3, decreased protein expression of Bcl-2. Meantime, OTA treatment triggered autophagy, as indicated by markedly increased the protein expression of LC3-II and fluorescence intensity of GFP-LC3 dots. Taurine supplementation decreased OTA-induced cytotoxicity and attenuated apoptosis as shown by the decreased Annexin V/PI staining and the decreased expression of apoptosis-related proteins including Bax and caspase-3. Meanwhile, taurine attenuated OTA-induced autophagy by decreased the protein expression of LC3-II and fluorescence intensity of GFP-LC3 dots to maintain cellular homeostasis. In conclusion, taurine treatment could alleviate OTA-induced apoptosis and inhibit the triggered autophagy in PK-15 cells. Our study provides supportive data for the potential roles of taurine in reducing OTA-induced renal toxicity.