The molecular mechanism of G2/M cell cycle arrest induced by AFB1 in the jejunum

Abstract

Aflatoxin B1 (AFB1) has potent hepatotoxic, carcinogenic, genotoxic, immunotoxic and other adverse effects in human and animals. The aim of this study was to investigate the molecular mechanism of G2/M cell cycle arrest induced by AFB1 in the jejunum of broilers. Broilers, as experimental animals, were fed 0.6 mg/kg AFB1 diet for 3 weeks. Our results showed that AFB1 reduced the jejunal villus height, villus height/crypt ratio and caused G2/M cell cycle arrest. The G2/M cell cycle was accompanied by the increase of ataxia telangiectasia mutated (ATM), p53, Chk2, p21 protein and mRNA expression, and the decrease of Mdm2, cdc25C, cdc2, cyclin B and proliferating cell nuclear antigen protein and mRNA expression. In conclusion, AFB1 blocked G2/M cell cycle by ATM pathway in the jejunum of broilers.

Sodium selenite prevents suppression of mucosal humoral response by AFB1 in broiler’s cecal tonsil

“…However, it is interesting to find that under light microscope, no shedding of the absorptive cells in the villi of cecal tonsils was observed in the AFB 1 group, which is consistent with Ledoux's report in the small intestine, when male broilers were exposed to 4 mg /kg AFB 1 for 3 weeks [ 26 ]. However, this result is different from early researches in the jejunum in which the shedding of the absorptive cells occurred on the apical region of villi in the broilers exposure to 0.3 or 0.6 mg/kg AFB 1 [ 27 , 28 ]. This discrepancy may be related to the different segments of gastrointestinal tract or AFB 1 concentration.…”

Chronic and Acute Toxicities of Aflatoxins: Mechanisms of Action

“…These findings were recently corroborated by feeding broiler chicken with feed containing 0.6 mg AFB1/kg for up to 21 days and monitoring structural and functional changes in the small intestine [128]. The study showed various structural and histopathological injuries similar to those described above regarding the increased depth of villi with decreased height and area [127], in addition to other histopathological alterations in the small intestine, including mitochondrial vacuolation and loss of cristae, reduced numbers of the absorptive cell goblets and the junctional complexes. Such changes dramatically alter the barrier function of the intestine to interfere not only with nutrient absorption, but also with the innate immune response as a protective means against the invasion of pathogens or toxins.…”

“…Aflatoxins have also been demonstrated to disrupt the integrity and function of the mechanical barrier of intestines by interfering with the cell cycle progression or by destroying the intestinal epithelial cells and the tight junctions (TJs) that cement them together. Administration of 0.6 mg AFB1/kg diet to broilers for 3 weeks stalled the cell cycle at the G2/M phase causing a reduction in the height jejunum and in the ratio of villus height/crypt, thereby impairing their function as a selective barrier [127]. These findings were recently corroborated by feeding broiler chicken with feed containing 0.6 mg AFB1/kg for up to 21 days and monitoring structural and functional changes in the small intestine [128].…”

Identification of Key Genes and Molecular Mechanisms Associated With Docetaxel Resistance in Castration Resistant Prostate Cancer Based on Bioinformatics Analysis

“…MYC proto-oncogene is reported as an oncogenic transcription factor, promotion of the cell cycle is the major oncogenic mechanism [22], and it has been reported that N-Myc (one of the MYC family) differentially regulating miR-421/ATM pathway contributes to ADT and enzalutamide resistance [23]. The "G2M checkpoint" and "MITOTIC spindle" are gene sets involved in cell cycle [24,25]. These results indicate that TUBB4A and CSRP2 may participate in docetaxel resistance by E2F transcription factor and MYC protooncogene in the process of cell cycle.…”