title: Trinitrotoluene Induces Endoplasmic Reticulum Stress and Apoptosis in HePG2 Cells.
abstract: BACKGROUND
  This study aims to describe trinitrotoluene (TNT)-induced endoplasmic reticulum stress (ERS) and apoptosis in HePG2 cells.
  
  
  METHODS
  HePG2 cells were cultured in vitro with 0, 6, 12, or 24 μg/ml TNT solution for 12, 24, and 48 h. Western blotting was performed to detect intracellular ERS-related proteins, including glucose-regulated protein (GRP) 78, GRP94, Caspase 4, p-Jun N-terminal kinase (JNK), and C/EBP homologous protein (CHOP). Real-time PCR was used to measure mRNA expression from the respective genes.
  
  
  RESULTS
  The expressions of ERS-related proteins GRP78 and GRP94 as well as mRNA and protein expression of ERS signaling apoptotic CHOP in the TNT treatment group were significantly increased. In addition, the mRNA and protein expression levels of ERS-induced apoptotic protein Caspase-4 were significantly increased. Flow cytometry revealed that after TNT treatment, the apoptosis rate also significantly increased.
  
  
  CONCLUSIONS
  TNT could increase the expression levels of GRP78, GRP94, Caspase-4, and CHOP in HePG2 cells; this increase in protein expression might be involved in HePG2 apoptosis through the induction of the ERS pathway.
authors.affiliation: Department of Occupational and Environmental Health, School of Public Health, Harbin Medical University, Harbin, Heilongjiang, China (mainland).
authors.forename: Li
authors.initials: L
authors.lastname: Song
authors.affiliation: Department of Occupational and Environmental Health, School of Public Health, Harbin Medical University, Harbin, Heilongjiang, China (mainland).
authors.forename: Yue
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Occupational and Environmental Health, School of Public Health, Harbin Medical University, Harbin, Heilongjiang, China (mainland).
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Occupational Poisoning, Heilongjiang Institute of Labor, Health, and Occupational Disease, Harbin, Heilongjiang, China (mainland).
authors.forename: Fan
authors.initials: F
authors.lastname: Yang
authors.affiliation: Department of Occupational and Environmental Health, Heilongjiang Institute of Labor, Health, and Occupational Disease, Harbin, Heilongjiang, China (mainland).
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Occupational and Environmental Health, School of Public Health, Harbin Medical University, Harbin, Heilongjiang, China (mainland).
authors.forename: Yonghui
authors.initials: Y
authors.lastname: Wu
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D053471:Caspases, Initiator / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D005434:Flow Cytometry; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D020287:In Situ Nick-End Labeling; D008562:Membrane Glycoproteins / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D048055:Mitogen-Activated Protein Kinase 8 / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D051742:Transcription Factor CHOP / Q000378:metabolism; D014303:Trinitrotoluene / Q000737:chemistry*
chemical_list: C497249:DDIT3 protein, human; D000091342:Endoplasmic Reticulum Chaperone BiP; D018840:HSP70 Heat-Shock Proteins; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D012333:RNA, Messenger; C053387:endoplasmin; C018551:glucose-regulated proteins; D014303:Trinitrotoluene; D051742:Transcription Factor CHOP; D048055:Mitogen-Activated Protein Kinase 8; C093516:CASP4 protein, human; D053471:Caspases, Initiator