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 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.
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 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: G A Pena; M P Monge; M L González Pereyra; A M Dalcero; C A R Rosa; S M Chiacchiera; L R Cavaglieri Journal: Mycotoxin Res Date: 2015-05-16 Impact factor: 3.833
Authors: Yigit S Guner; Christian J Ochoa; Jin Wang; Xiaoru Zhang; Sarah Steinhauser; Lydia Stephenson; Anatoly Grishin; Jeffrey S Upperman Journal: Biochem Biophys Res Commun Date: 2009-04-23 Impact factor: 3.575
Authors: M Pellegrino; V Alonso; C Vissio; A Larriestra; S M Chiacchiera; C Bogni; L Cavaglieri Journal: Mycotoxin Res Date: 2013-03-07 Impact factor: 3.833