Ochratoxin A (OTA) is a fungal toxin that causes serious threat to human health. OTA could lead to the injury of various tissues, especially kidney injury. However, the toxic effects of OTA on human kidney tubular epithelial cell (HK-2) and the possible mechanism remains poorly understood. This study was to investigate the toxic effects of OTA on HK-2 and elucidate the molecular mechanism. HK-2 cells were treated OTA to evaluate the effect of OTA on cell viability and apoptosis. OTA inhibited the growth of HK-2 in a concentration-dependent manner. With the concentration increased, OTA significantly lead to the apoptosis of HK-2. OTA could increase the levels of reactive oxygen species (ROS) and Malondialdehyde (MDA). Superoxide dismutase (SOD) and glutathione (GSH) activities were decreased by OTA. Furthermore, OTA increased Caspase-3 and Bax expression and decreased BCL2 expression. Compared to the control group, the expression of PTEN was increased and the expression of PI3K and AKT were decreased in OTA treated groups. In addition, we found OTA could disrupt the formation of lipid raft by attenuating sphingomyelin and cholesterol levels. In conclusion, our results indicated that OTA induces apoptosis in HK-2 through regulating PTEN/AKT signaling pathway via disrupting lipid raft formation.

中文翻译：

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赭曲霉毒素A通过调节脂筏/PTEN/AKT信号通路诱导人肾小管上皮细胞凋亡

Ochratoxin A (OTA) 是一种真菌毒素，对人类健康造成严重威胁。OTA可能导致各种组织的损伤，尤其是肾损伤。然而，OTA对人肾小管上皮细胞（HK-2）的毒性作用及其可能的机制仍知之甚少。本研究旨在研究O​​TA对HK-2的毒性作用并阐明其分子机制。OTA 处理 HK-2 细胞以评估 OTA 对细胞活力和细胞凋亡的影响。OTA 以浓度依赖性方式抑制 HK-2 的生长。随着浓度的增加，OTA显着导致HK-2的凋亡。OTA 可以增加活性氧 (ROS) 和丙二醛 (MDA) 的水平。OTA 降低了超氧化物歧化酶 (SOD) 和谷胱甘肽 (GSH) 的活性。此外，OTA 增加 Caspase-3 和 Bax 表达并降低 BCL2 表达。与对照组相比，OTA治疗组PTEN表达增加，PI3K和AKT表达降低。此外，我们发现 OTA 可以通过降低鞘磷脂和胆固醇水平来破坏脂筏的形成。总之，我们的结果表明，OTA 通过破坏脂筏形成来调节 PTEN/AKT 信号通路，从而诱导 HK-2 细胞凋亡。