| Autor: |
Arumugam T; Discipline of Medical Biochemistry and Chemical Pathology, School of Laboratory Medicine and Medical Sciences, College of Health Sciences, University of KwaZulu-Natal, George Campbell Building, Howard College, Durban, 4041, South Africa., Ghazi T; Discipline of Medical Biochemistry and Chemical Pathology, School of Laboratory Medicine and Medical Sciences, College of Health Sciences, University of KwaZulu-Natal, George Campbell Building, Howard College, Durban, 4041, South Africa., Chuturgoon AA; Discipline of Medical Biochemistry and Chemical Pathology, School of Laboratory Medicine and Medical Sciences, College of Health Sciences, University of KwaZulu-Natal, George Campbell Building, Howard College, Durban, 4041, South Africa. chutur@ukzn.ac.za. |
| Jazyk: |
angličtina |
| Zdroj: |
Archives of toxicology [Arch Toxicol] 2021 Apr; Vol. 95 (4), pp. 1367-1378. Date of Electronic Publication: 2021 Jan 26. |
| DOI: |
10.1007/s00204-021-02986-5 |
| Abstrakt: |
FB 1 is a common contaminant of cereal grains that affects human and animal health. It has become increasingly evident that epigenetic changes are implicated in FB 1 toxicity. N6-methyladenosine (m6A), the most abundant post-transcriptional RNA modification, is influenced by fluctuations in redox status. Since oxidative stress is a characteristic of FB 1 exposure, we determined if there is cross-talk between oxidative stress and m6A in FB 1 -exposed HepG2 cells. Briefly, HepG2 cells were treated with FB 1 (0, 5, 50, 100, 200 µM; 24 h) and ROS, LDH and m6A levels were quantified. qPCR was used to determine the expression of m6A modulators, Nrf2, Keap1 and miR-27b, while western blotting was used to quantify Keap1 and Nrf2 protein expression. Methylation status of Keap1 and Nrf2 promoters was assessed and RNA immunoprecipitation quantified m6A-Keap1 and m6A-Nrf2 levels. FB 1 induced accumulation of intracellular ROS (p ≤ 0.001) and LDH leakage (p ≤ 0.001). Elevated m6A levels (p ≤ 0.05) were accompanied by an increase in m6A "writers" [METLL3 (p ≤ 0.01) and METLL14 (p ≤ 0.01)], and "readers" [YTHDF1 (p ≤ 0.01), YTHDF2 (p ≤ 0.01), YTHDF3 (p ≤ 0.001) and YTHDC2 (p ≤ 0.01)] and a decrease in m6A "erasers" [ALKBH5 (p ≤ 0.001) and FTO (p ≤ 0.001)]. Hypermethylation and hypomethylation occurred at Keap1 (p ≤ 0.001) and Nrf2 (p ≤ 0.001) promoters, respectively. MiR-27b was reduced (p ≤ 0.001); however, m6A-Keap1 (p ≤ 0.05) and m6A-Nrf2 (p ≤ 0.01) levels were upregulated. This resulted in the ultimate decrease in Keap1 (p ≤ 0.001) and increase in Nrf2 (p ≤ 0.001) expression. Our findings reveal that m6A RNA methylation can be modified by exposure to FB 1 , and a cross-talk between m6A and redox regulators does occur. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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