Mechanism of intestinal-derived fungal sepsis by gliotoxin, a fungal metabolite

Jeffrey S. Upperman, Douglas A. Potoka, Xiao Ru Zhang, Katerina Wong, Ruben Zamora, Henri Ford

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Background/Purpose: 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 pancaspase 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.

Original languageEnglish (US)
Pages (from-to)966-970
Number of pages5
JournalJournal of Pediatric Surgery
Volume38
Issue number6
DOIs
StatePublished - Jun 1 2003
Externally publishedYes

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Gliotoxin
Sepsis
Enterocytes
Apoptosis
Caspase 3
Poly(ADP-ribose) Polymerases

Keywords

  • Apoptosis
  • Bacterial translocation
  • Enterocytes
  • Fungal sepsis
  • Gliotoxin

ASJC Scopus subject areas

  • Surgery
  • Pediatrics, Perinatology, and Child Health

Cite this

Mechanism of intestinal-derived fungal sepsis by gliotoxin, a fungal metabolite. / Upperman, Jeffrey S.; Potoka, Douglas A.; Zhang, Xiao Ru; Wong, Katerina; Zamora, Ruben; Ford, Henri.

In: Journal of Pediatric Surgery, Vol. 38, No. 6, 01.06.2003, p. 966-970.

Research output: Contribution to journalArticle

Upperman, Jeffrey S. ; Potoka, Douglas A. ; Zhang, Xiao Ru ; Wong, Katerina ; Zamora, Ruben ; Ford, Henri. / Mechanism of intestinal-derived fungal sepsis by gliotoxin, a fungal metabolite. In: Journal of Pediatric Surgery. 2003 ; Vol. 38, No. 6. pp. 966-970.
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AU - Ford, Henri

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