活性氧介导的赭曲霉毒素 A 诱导肾小管上皮细胞凋亡选择性激活内质网应激。
Selective Activation of Endoplasmic Reticulum Stress by Reactive-Oxygen-Species-Mediated Ochratoxin A-Induced Apoptosis in Tubular Epithelial Cells.
机构信息
Graduate Institute of Toxicology, College of Medicine, National Taiwan University, Taipei 10617, Taiwan.
Department of Anesthesiology, Far-Eastern Memorial Hospital, New Taipei City 22060, Taiwan.
出版信息
Int J Mol Sci. 2021 Oct 11;22(20):10951. doi: 10.3390/ijms222010951.
Ochratoxin A (OTA), one of the major food-borne mycotoxins, impacts the health of humans and livestock by contaminating food and feed. However, the underlying mechanism of OTA nephrotoxicity remains unknown. This study demonstrated that OTA induced apoptosis through selective endoplasmic reticulum (ER) stress activation in human renal proximal tubular cells (HK-2). OTA increased ER-stress-related JNK and precursor caspase-4 cleavage apoptotic pathways. Further study revealed that OTA increased reactive oxygen species (ROS) levels, and N-acetyl cysteine (NAC) could reduce OTA-induced JNK-related apoptosis and ROS levels in HK-2 cells. Our results demonstrate that OTA induced ER stress-related apoptosis through an ROS-mediated pathway. This study provides new evidence to clarify the mechanism of OTA-induced nephrotoxicity.
赭曲霉毒素 A（OTA）是主要的食源性真菌毒素之一，通过污染食物和饲料影响人类和牲畜的健康。然而，OTA 肾毒性的潜在机制尚不清楚。本研究表明，OTA 通过选择性内质网（ER）应激激活诱导人肾近端小管细胞（HK-2）凋亡。OTA 增加了与 ER 应激相关的 JNK 和前体半胱天冬酶-4 切割凋亡途径。进一步的研究表明，OTA 增加了活性氧（ROS）水平，N-乙酰半胱氨酸（NAC）可以减少 OTA 诱导的 HK-2 细胞中 JNK 相关的凋亡和 ROS 水平。我们的结果表明，OTA 通过 ROS 介导的途径诱导 ER 应激相关的凋亡。本研究为阐明 OTA 诱导的肾毒性机制提供了新的证据。
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