Date: Sunday, May 3, 2015
Session Time: 5:30pm-6:30pm
Presentation Time: 5:30pm-6:30pm
Location: Exhibit Hall E
Organs from brain dead donors have inferior quality and show higher rejection rates after transplantation compared to living donors. Brain death (BD) in the donor results in increased tissue injury and apoptosis. Apoptosis is closely linked to autophagy, a stress-adaptation mechanism to avoid cell death. Dysregulation of autophagy has been linked to a number of diseases that show molecular resemblances to the BD setting, such as ischemia/reperfusion-injury and sepsis. This study aimed to investigate autophagy in the BD setting, by looking at the dynamics between autophagy, apoptosis, and tissue injury in the kidney and liver of brain dead rats.
BD was induced in mechanically ventilated rats by inflation of a Fogarty catheter in the epidural space. After 4 hrs of BD, serum, kidney, and liver tissue were collected. Routine biochemistry was performed, as well as RT-qPCR for apoptotic genes BAX and Bcl-2, and autophagy genes LC3, Beclin 1, and p62, immunohistochemistry for apoptosis-effector cleaved Caspase 3 (cC3), and Western-blot (WB) analyses for autophagy proteins (LC3-I, LC3-II, p62, pS6) and apoptosis protein cC3.
Brain dead animals had increased ASAT, ALAT, creatinine, and urea plasma levels. In the kidney, BD reduced levels of autophagic marker LC3-lI, and increased activation of autophagy-inhibitor mTOR, which significantly correlated with increased levels of apoptosis protein cC3. In the liver, BD increased gene expression of BAX and BAX/Bcl-2 ratio, as well as cC3 expression. However, signs of increased apoptosis or affected autophagy were not observed on a protein level in the liver.
BD causes tissue injury in the liver and kidney of brain dead rats. However, BD had differential effects on autophagy in the liver and the kidney. While a decrease in autophagy correlated with increased apoptosis in the kidney, autophagy was not significantly altered in the liver. These results suggest a possible role for autophagy in protection against BD-induced kidney damage.
To cite this abstract in AMA style:Erp Avan, Rebolledo R, Ottens P, Pirenne J, Leuvenink H, Decuypere J-P. Down-Regulation of Autophagy Correlates With Increased Apoptosis in the Kidney, But Not in the Liver, of Brain Dead Rats [abstract]. Am J Transplant. 2015; 15 (suppl 3). https://atcmeetingabstracts.com/abstract/down-regulation-of-autophagy-correlates-with-increased-apoptosis-in-the-kidney-but-not-in-the-liver-of-brain-dead-rats/. Accessed May 31, 2020.
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