ABSTRACT
Trichloroethylene (TCE) was a widely used industrial solvent, and now has become a major environmental pollutant. Exposure to TCE has been found to result in significant damage to the liver, leading to hepatic toxicity. In our previous study, we discovered that a histone chaperon called SET plays a crucial role in mediating the DNA damage and apoptosis caused by TCE in hepatic cells. However, the precise function of SET in the response to DNA damage is still not fully understood. In this study, we evaluated TCE-induced DNA damage of hepatic L-02 cells with SET-knockdown, then analyzed alterations of H3K79me3 and p53 in hepatic cells and carcinogenic mice livers. Results suggested that SET interferes with DNA response via mediating down-regulation of p53 and partially suppressing H3K79me3 under treatment of TCE. To further verify the regulatory cascade, H3K79me3 was reduced and p53 was knocked down in L-02 cells respectively, and extent of DNA damage was evaluated. Reduced H3K79me3 was found leading to down-regulation of p53 which further exacerbated TCE-induced DNA injury. These findings demonstrated that SET-H3K79me3-p53 served as an epigenetic regulatory axis involved in TCE-induced DNA damage response.
Subject(s)
DNA Damage , Epigenesis, Genetic , Trichloroethylene , Tumor Suppressor Protein p53 , Animals , Mice , Hepatocytes/drug effects , Hepatocytes/metabolism , Trichloroethylene/toxicity , Tumor Suppressor Protein p53/genetics , DNA Damage/geneticsABSTRACT
Foodborne illness outbreaks can be caused by a great many of gastrointestinal microorganisms including bacteria, viruses and parasites. Acute gastroenteritis is most commonly found in such patients infected with at least one pathogen through food intake. The stool culture has been conventionally used to guide a single diagnosis and therapy. However, traditional methods for identification of a pathogen are time-consuming and have limited sensitivity, leading to false negatives and co-infection omission. The aim of this study was to characterize the multiple etiology of each foodborne illness outbreak in Shenzhen during 2018-2019 by the FilmArray GI panel, and to reveal the seasonality of each causative organism incurring outbreaks. All patients included had a FilmArray GI panel performance and the seasonal characteristics were recorded. A total of 173 patients suffered from foodborne illnesses in 32 outbreaks in Nanshan District of Shenzhen. In total, 365 microorganisms were detected of which 83.8% (306/365) corresponded to bacteria and 16.2% (59/365) to viruses. Co-infections with more than one microorganism were detected in 81.3% (26/32) of the outbreaks. In 153 (88.4%) of 173 patients at least two pathogens were identified. The most common diarrheal pathogen related to outbreaks was EPEC (56%), followed by ETEC (38%), Norovirus (34%), EAEC (28%), Vibrio (25%), Salmonella (22%), P. shigelloides (22%), C. difficile (16%), STEC (3%) and Sapovirus (3%). Bacterial outbreaks occurred with a seasonal distribution with the exception of C. difficile whereas Norovirus outbreaks predominated during the autumn-winter months. The use of the FilmArray GI panel has given us worthy information regarding the epidemiology of pathogens detected in patients with acute diarrhea. It also highlights the importance of multi-pathogen infections and the frequency of diarrheogenic E. coli in foodborne disease outbreaks. More significantly, the rapid and multiple findings may help quickly taking an appropriate precaution, control and treatment.
Subject(s)
Disease Outbreaks , Foodborne Diseases/epidemiology , Foodborne Diseases/microbiology , Gastroenteritis/epidemiology , Gastroenteritis/microbiology , Gastrointestinal Microbiome , Molecular Diagnostic Techniques , China/epidemiology , Foodborne Diseases/diagnosis , Foodborne Diseases/history , Gastroenteritis/diagnosis , Gastroenteritis/history , History, 21st Century , Humans , Molecular Diagnostic Techniques/methods , Multiplex Polymerase Chain Reaction , SeasonsABSTRACT
Trichloroethylene (TCE) is a ubiquitous toxicant widespread in our environment. Exposure to TCE can cause severe liver damage. In previous studies, we detected an abnormal elevation of SET (a protein encoded by the SETgene in humans) which was observed in human HL-7702 cells (L-02 hepatocytes) under the treatment of TCE. Moreover, further study indicated that SET acts as an important mediator in TCE-induced hepatocyte apoptosis. The major functions of SET have been elucidated, while the regulatory mechanism responsible for modulation of SET remains unclear. In this study, four major microRNA-related databases were used to screen and identify 6 candidate microRNAs involved in the regulation of SET. Subsequent verification indicated that miR-21 and miR-199b-5p were decreased in TCE-treated L-02 cells, suggesting that miR-21 and miR-199b-5p (miR199b for short) miR199b potentially regulate SET expression. Additionally, the dual-luciferase system revealed that only miR199b could directly bind to untranslated region (3'-UTR) of the SETgene. Modulation of SET by miR199b was verified through overexpression and knockdown of miR199b in L-02 cells. Assessment of apoptosis indicated that elevated miR199b attenuated TCE-induced apoptosis, while reduced miR199b enhanced it. In summary, this study suggests that in cultured hepatocytes, TCE-induced suppression of miR199b drives SET induction, which further mediates the response to TCE.
