title: Dengue 2 infection of HepG2 liver cells results in endoplasmic reticulum stress and induction of multiple pathways of cell death.
abstract: BACKGROUND
  A number of studies have implicated the direct involvement of the liver in dengue virus (DENV) infection, and it has been widely shown that liver cells subsequently undergo apoptosis. The mechanism by which liver cells undergo apoptosis in response to DENV infection remains unclear. To provide further information on the mechanism of apoptosis in DENV infected liver cells, HepG2 cells were infected with DENV 2 and analyzed for the induction of ER stress, apoptosis and autophagy.
  
  
  RESULTS
  In response to DENV infection, HepG2 cells showed the induction of both the ER resident unfolded protein response as well as the Noxa/PUMA stress response pathways. Proteolytic activation of caspases 4, 7, 8 and 9 was observed as well as changes in mitochondrial transmembrane potential. Increased monodansylcadaverine staining was observed in DENV infected cells, consistent with the previously reported induction of autophagy.
  
  
  CONCLUSIONS
  These results are consistent with a model in which the induction of multiple ER stress pathways is coupled with the induction of multiple cell death pathways as a mechanism to ensure the removal of infected liver cells from the system.
authors.affiliation: Molecular Pathology Laboratory, Institute of Molecular Biosciences, Mahidol University, 25/25 Phuttamontol Sai 4, Salaya, Nakorn Pathom 73170, Thailand. duncan_r_smith@hotmail.com.
authors.forename: Chutima
authors.initials: C
authors.lastname: Thepparit
authors.forename: Atefeh
authors.initials: A
authors.lastname: Khakpoor
authors.forename: Sarawut
authors.initials: S
authors.lastname: Khongwichit
authors.forename: Nitwara
authors.initials: N
authors.lastname: Wikan
authors.forename: Chanida
authors.initials: C
authors.lastname: Fongsaran
authors.forename: Pimjai
authors.initials: P
authors.lastname: Chingsuwanrote
authors.forename: Patcharee
authors.initials: P
authors.lastname: Panraksa
authors.forename: Duncan R
authors.initials: DR
authors.lastname: Smith
mesh_terms: D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D001343:Autophagy / Q000235:genetics; D020169:Caspases / Q000378:metabolism; D016923:Cell Death; D002470:Cell Survival / Q000235:genetics; D003715:Dengue / Q000473:pathology* / Q000821:virology*; D003716:Dengue Virus / Q000502:physiology*; D059865:Endoplasmic Reticulum Stress; D004789:Enzyme Activation; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D006801:Humans; D008099:Liver / Q000201:enzymology / Q000473:pathology* / Q000821:virology*; D053078:Membrane Potential, Mitochondrial; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics / Q000378:metabolism; D051742:Transcription Factor CHOP / Q000378:metabolism; D056811:Unfolded Protein Response
chemical_list: D051017:Apoptosis Regulatory Proteins; C438378:BBC3 protein, human; C498702:PMAIP1 protein, human; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D053221:TNF-Related Apoptosis-Inducing Ligand; D051742:Transcription Factor CHOP; D020169:Caspases
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