Exposure to Penicillium mycotoxins alters gene expression of enzymes involved in the epigenetic regulation of bovine macrophages (BoMacs)

• Published in: Mycotoxin research Vol. 29; no. 4; pp. 235 - 243
• Main Authors: Oh, Se-Young, Balch, Caroline G, Cliff, Rachael L, Sharma, Bhawani S, Boermans, Herman J, Swamy, H. V. L. N, Quinton, V. Margaret, Karrow, Niel A
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer-Verlag 01.11.2013; Springer Berlin Heidelberg; Springer; Springer Nature B.V
• Subjects: Animals; Biological and medical sciences; Biomedical and Life Sciences; Bmi protein; Cattle; Chemistry/Food Science; citrinin; Enzymes; Epigenesis, Genetic - drug effects; Epigenesis, Genetic - physiology; Epigenetics; Fundamental and applied biological sciences. Psychology; Gene expression; histone deacetylase; Histone Deacetylases - genetics; Histone Deacetylases - metabolism; Histone Demethylases - genetics; Histone Demethylases - metabolism; Life Sciences; macrophages; Macrophages - enzymology; Macrophages - metabolism; Medical Microbiology; Medicine/Public Health; Methyltransferases - genetics; Methyltransferases - metabolism; Microbiology; Mycology; Mycotoxins - metabolism; ochratoxin A; Original Paper; Pathogenicity, host-agent relations, miscellaneous strains, epidemiology; patulin; penicillic acid; Penicillium; Penicillium - metabolism; quantitative polymerase chain reaction; Real-Time Polymerase Chain Reaction; RNA - chemistry; RNA - genetics; Toxins; Mycophenolic acid; Penicillic acid; Bovine macrophage; Epigenetics; Citrinin; Ochratoxin A; Patulin; Penicillium Mycotoxins; Ochratoxin; Penicillium; Mycotoxin; Fungi; Regulation(control); Fungi Imperfecti; Ungulata; Bovine; Enzyme; Exposure; Gene expression; Toxin; Vertebrata; Antibiotic; Mammalia; Artiodactyla; Macrophage
• ISSN: 0178-7888; 1867-1632
• DOI: 10.1007/s12550-013-0174-y

In this study, the modulation of key enzymes involved in epigenetic regulation was assessed in immortalized bovine macrophages (BoMacs) following in vitro exposure to the following Penicillium mycotoxins: citrinin (CIT), ochratoxin A (OTA), patulin (PAT), mycophenolic acid (MPA), penicillic acid (PA), or a combination of one of the above with OTA at the concentration that inhibits BoMac proliferation by 25 % (IC25). Real-time PCR analysis of the genes coding DNA methyltransferases (DNMTs), histone demethylases (JMJD-3 and UTX), as well as the class-1 histone deacetylases (HDAC−1, −2, and −3) and histone acetylase (Bmi-1) was assessed following 6 h of mycotoxin exposure. A change in the expression of JMJD-3 as well as HDAC-3, MPA (p = 0.1) and PA (p = 0.08), by at least one of the treatments was observed at their respective IC25. The expression of JMJD-3 was significantly induced by PA, but synergistically suppressed by CIT + OTA. The combination of CIT + OTA also synergistically suppressed the expression of DNMT-3a and DNMT-3b. The combination of PAT + OTA reduced DNMT-3a expression, while PA + OTA reduced DNMT-3b expression. Lastly, MPA and PA slightly reduced HDAC-3 expression, while OTA in combination with CIT, PAT, MPA or PA synergistically suppressed HDAC-3 expression. The results of this study demonstrate that Penicillium mycotoxin exposure, specifically OTA and other mycotoxin combinations, can alter the expression of BoMac enzymes that are involved in epigenetic regulation. These findings suggest a potential novel regulatory mechanism by which mycotoxins can modulate macrophage function.