title: Deoxycholic acid inhibited proliferation and induced apoptosis and necrosis by regulating the activity of transcription factors in rat pancreatic acinar cell line AR42J.
abstract: The objective of this study is to investigate the effect of deoxycholic acid (DCA) on rat pancreatic acinar cell line AR42J and the functional mechanisms of DCA on AR42J cells. AR42J cells were treated with various concentrations of DCA for 24 h and also treated with 0.4 mmol/L DCA for multiple times, and then, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was performed to detect the AR42J cell survival rate. Flow cytometric was used to detect the cell apoptosis and necrosis in AR42J cells treated with 0.4 mmol/L and 0.8 mmol/L DCA. The cells treated with phosphate buffer saline (PBS) were served as control. In addition, the DNA-binding activity assays of transcription factors (TFs) in nuclear proteins of cells treated with DCA were determined using Panomics Procarta Transcription Factor Assay Kit. The relative survival rates were markedly decreased (P < 0.05) in a dose- and time-dependent manner. Compared with control group, the cell apoptosis and necrosis ratio were both significantly elevated in 0.4 mmol/L DCA and 0.8 mmol/L DCA groups (P < 0.01). A significant increase (P < 0.05) in the activity of transcription factor 2 (ATF2), interferon-stimulated response element (ISRE), NKX-2.5, androgen receptor (AR), p53, and hypoxia-inducible factor-1 (HIF-1) was observed, and the activity of peroxisome proliferator-activated receptor (PPAR), activator protein 1 (AP1), and E2F1 was reduced (P < 0.05). In conclusion, DCA inhibited proliferation and induced apoptosis and necrosis in AR42J cells. The expression changes of related genes regulated by TFs might be the molecular mechanism of AR42J cell injury.
authors.affiliation: Department of General Surgery, First Affiliated Hospital of Dalian Medical University, Zhongshan Road 222, Dalian, China, 116011. guixinzhanggxz@163.com.
authors.forename: Guixin
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Department of General Surgery, First Affiliated Hospital of Dalian Medical University, Zhongshan Road 222, Dalian, China, 116011. jingwenzhangjwz@163.com.|Dalian Medical University, Dalian, China, 116044. jingwenzhangjwz@163.com.
authors.forename: Jingwen
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of General Surgery, First Affiliated Hospital of Dalian Medical University, Zhongshan Road 222, Dalian, China, 116011. dongshangds@yeah.net.
authors.forename: Dong
authors.initials: D
authors.lastname: Shang
authors.affiliation: Department of General Surgery, First Affiliated Hospital of Dalian Medical University, Zhongshan Road 222, Dalian, China, 116011. bingqibq@126.com.
authors.forename: Bing
authors.initials: B
authors.lastname: Qi
authors.affiliation: Department of General Surgery, First Affiliated Hospital of Dalian Medical University, Zhongshan Road 222, Dalian, China, 116011. hailongchenhlc@163.com.
authors.forename: Hailong
authors.initials: H
authors.lastname: Chen
mesh_terms: D061354:Acinar Cells / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects*; D003840:Deoxycholic Acid / Q000494:pharmacology*; D005434:Flow Cytometry; D009336:Necrosis / Q000139:chemically induced; D010179:Pancreas / Q000166:cytology* / Q000473:pathology / Q000502:physiology; D051381:Rats; D014157:Transcription Factors / Q000187:drug effects / Q000502:physiology*
chemical_list: D014157:Transcription Factors; D003840:Deoxycholic Acid
keywords: Cell injury; Deoxycholic acid; Rat pancreatic acinar cell; Transcription factors