title: Mechanism of intestinal-derived fungal sepsis by gliotoxin, a fungal metabolite.
abstract: OBJECTIVE
  Gut barrier dysfunction resulting from fungal overgrowth may be caused by the interaction of gliotoxin (GT), a fungal metabolite, with enterocytes. The goal of this study was to determine the mechanisms by which gliotoxin (GT), a fungal metabolite, causes enterocyte apoptosis.
  
  
  METHODS
  The authors measured enterocyte apoptosis, caspase-3 activity, pro-caspase-3, and poly (ADP-ribose) polymerase (PARP) cleavage in GT-exposed IEC-6 cells, a rat intestinal cell line.
  
  
  RESULTS
  GT induced apoptosis in IEC-6 cells. The pan-caspase inhibitor ZVAD suppressed this GT-mediated apoptosis. GT induced a 15-fold increase in caspase-3 activity over media control. The authors detected PARP cleavage by after GT exposure. DTT pretreatment decreased apoptosis compared with GT alone.
  
  
  CONCLUSIONS
  This study supports the concept that fungal overgrowth may lead to gut barrier dysfunction by the local release of gliotoxin and the induction enterocyte apoptosis.
authors.affiliation: Department of Surgery, Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Upperman
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Potoka
authors.forename: Xiao-Ru
authors.initials: XR
authors.lastname: Zhang
authors.forename: Katerina
authors.initials: K
authors.lastname: Wong
authors.forename: Ruben
authors.initials: R
authors.lastname: Zamora
authors.forename: Henri R
authors.initials: HR
authors.lastname: Ford
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002177:Candidiasis / Q000382:microbiology / Q000473:pathology; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D005912:Gliotoxin / Q000037:antagonists & inhibitors / Q000097:blood / Q000378:metabolism* / Q000633:toxicity*; D007410:Intestinal Diseases / Q000382:microbiology* / Q000473:pathology; D051381:Rats; D018805:Sepsis / Q000382:microbiology* / Q000473:pathology; D013997:Time Factors
chemical_list: D005912:Gliotoxin