期刊
TOXICON
卷 199, 期 -, 页码 79-86出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.toxicon.2021.06.005
关键词
Ochratoxin A; NF-KB; HK-2 cell line; p-ERK1; 2; Apoptosis
资金
- Scientific and Technological Research Council of Turkey (TUBITAK) [114Z831]
OTA is a food contaminant mycotoxin that primarily affects kidney health in humans and animals. Research shows that OTA induces apoptosis by activating the NF-KB and MAPK/ERK signaling pathways, with NF-KB inhibition attenuating OTA-induced cell death.
Ochratoxin A (OTA) is a food contaminant mycotoxin with hazardous effects on human and animal health, primarily affecting the kidneys. OTA's mode of action is not well understood. OTA activates both MAPK/ERK and PI3K/Akt signaling pathways, which play role in apoptosis and cell survival, respectively. OTA is also known to induce toxicity by activating the NF-KB pathway in immune cells. However, its role in determining the cell fate upon OTA exposure in a human kidney cell line (HK-2) has not been fully explored. We made use of pharmacological inhibition of NF-KB to define its role in viability of OTA-treated HK-2 cells. We show that OTA-induced p65 NF-KB subunit translocation into the nucleus in a time-dependent manner using both Western blotting and immunofluorescence (IF). We also document the DNA-binding and reporter gene expression activities of NF-KB by electrophoretic mobility shift (EMSA) and luciferase reporter assays, respectively. Our results indicate that, following 6 h of exposure, OTA fully activates NF-KB pathway and its downstream effectors in HK-2 cells. In addition, Bay11-7085 treatment causes attenuation of the relative levels of OTA-mediated ERK1/2 phosphorylation, suggesting a cross-talk between NF-KB and the MAPK/ERK pathway. Critically, co-treatment of HK-2 cells with OTA and Bay11-7085 leads to the inhibition of OTA-induced apoptosis in a time-dependent manner. Our results support a robust association between NF-KB and the MAPK/ERK pathways in the modulation of apoptotic effects of OTA in HK-2 cells.
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