Ochratoxin A induces ERK1/2 phosphorylation-dependent apoptosis through NF-κB/ERK axis in human proximal tubule HK-2 cell line
Toxicon, cilt.199, ss.79-86, 2021 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 199
- Basım Tarihi: 2021
- Doi Numarası: 10.1016/j.toxicon.2021.06.005
- Dergi Adı: Toxicon
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Aerospace Database, Aquatic Science & Fisheries Abstracts (ASFA), BIOSIS, CAB Abstracts, Chemical Abstracts Core, Communication Abstracts, EMBASE, Environment Index, MEDLINE, Metadex, Pollution Abstracts, Veterinary Science Database, Civil Engineering Abstracts
- Sayfa Sayıları: ss.79-86
- Anahtar Kelimeler: Apoptosis, HK-2 cell line, NF-κB, Ochratoxin A, p-ERK1/2
- Boğaziçi Üniversitesi Adresli: Evet
Özet
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-κB 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-κB to define its role in viability of OTA-treated HK-2 cells. We show that OTA-induced p65 NF-κB 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-κB by electrophoretic mobility shift (EMSA) and luciferase reporter assays, respectively. Our results indicate that, following 6 h of exposure, OTA fully activates NF-κB 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-κB 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-κB and the MAPK/ERK pathways in the modulation of apoptotic effects of OTA in HK-2 cells.