title: Septic sera induces apoptosis and DNA fragmentation factor 40 activation in fibroblasts.
abstract: Sepsis, the systemic response to infection, is the leading cause of death in the intensive care units worldwide. Septic patients can succumb through the development of early refractory hypotension or late multiple organ dysfunction. Misregulation of apoptosis during sepsis may contribute to cellular dysfunction and multiple organ dysfunction. Utilizing a tissue culture model which mimics the human disease, we demonstrate that the addition of sera derived from septic patients induces apoptosis in human fibroblast cells. Addition of septic sera to 2fTGH cells induced apoptosis by activating caspase 8, caspase 3 and DNA fragmentation factor 40 (DFF 40). Interestingly, the addition of septic sera to cells which lack STAT1 (U3A cells) did not activate DFF 40. U3A cells were also shown to be resistant to septic serum induced apoptosis. These data suggest that DFF 40 mediated apoptosis plays a significant role in mediating sepsis induced cellular dysfunction.
authors.affiliation: Department of Chemistry and Biochemistry and The Biomolecular Sciences Programme, Laurentian University, Sudbury, ON, Canada P3E 2C6.
authors.forename: Danielle
authors.initials: D
authors.lastname: Brabant
authors.forename: Paul
authors.initials: P
authors.lastname: Michael
authors.forename: Farag
authors.initials: F
authors.lastname: Bleiblo
authors.forename: Mazen
authors.initials: M
authors.lastname: Saleh
authors.forename: Ravin
authors.initials: R
authors.lastname: Narain
authors.forename: T C
authors.initials: TC
authors.lastname: Tai
authors.forename: Chilakamarti V
authors.initials: CV
authors.lastname: Ramana
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Parrillo
authors.forename: Anand
authors.initials: A
authors.lastname: Kumar
authors.forename: Aseem
authors.initials: A
authors.lastname: Kumar
mesh_terms: D017209:Apoptosis; D053181:Caspase 8 / Q000378:metabolism; D002460:Cell Line; D003851:Deoxyribonucleases / Q000378:metabolism*; D005347:Fibroblasts / Q000201:enzymology / Q000473:pathology*; D006801:Humans; D000075223:Poly-ADP-Ribose Binding Proteins; D018805:Sepsis / Q000097:blood / Q000201:enzymology* / Q000473:pathology*; D044967:Serum / Q000382:microbiology*
chemical_list: D000075223:Poly-ADP-Ribose Binding Proteins; C113696:DFFB protein, human; D003851:Deoxyribonucleases; D053181:Caspase 8