Hepatic autophagy after severe burn in response to endoplasmic reticulum stress

被引:21
|
作者
Song, Juquan [1 ]
de Libero, Jana [1 ]
Wolf, Steven E. [1 ]
机构
[1] Univ Texas SW Med Ctr Dallas, Dept Surg, Div Burn Trauma Crit Care, Dallas, TX 75390 USA
关键词
Thermal injury; Mouse liver; Endoplasmic reticulum (ER); Autophagy; Apoptosis; RESISTANCE; INJURY; TRAUMA; KINASE;
D O I
10.1016/j.jss.2013.09.042
中图分类号
R61 [外科手术学];
学科分类号
摘要
Background: Previous studies showed that liver dysfunction develops soon after severe burn, and this is associated with activation of endoplasmic reticulum (ER) stress. Autophagy is a catabolic process to maintain cellular organelle balance; ER stress is associated with autophagy signaling cascades. We thus sought to determine whether autophagy signals were associated with damage in the liver after burn, and further whether burn-associated ER stress activates autophagy signals in hepatocytes. Methods: C57BL/6 male mice received a 25% total body surface area full-thickness scald burn, and liver was harvested at 24 h after burn. HepG2 cells were stimulated with an ER stress inducer thapsigargin (TG) for 24 h to mimic ER stress in vitro. Terminal deoxyuridine nick-end labeling staining was performed on histologic sections of liver. Autophagy was assessed by immunoblotting. Statistical analysis was performed using the Student t-test and significance was accepted at P < 0.05. Results: Terminal deoxyuridine nick-end labeling positive-stained hepatocytes increased in burned animalswith a significant elevation of caspase 3 activity (P < 0.05). Hepatic autophagy-related (ATG) protein 3, ATG5 and light chain (LC) 3B elevated significantly in burn animals as well (P < 0.05). Expression of Beclin-1, LC3A, and LC3B increased in HepG2 cells in response to TG, similar to the response seenin vivo. Cytosolic adenosine triphosphate dropped significantly, and adenosine monophosphate activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) were phosphorylated as well in response to TG (P < 0.05). Conclusions: ER stress, which occurs in hepatocytes after severe injury, is associated with autophagy and liver damage after severe burn. In response to ER stress, activated autophagy is associated with adenosine monophosphateeactivated protein kinase and mammalian target target of rapamycin pathway. (C) 2014 Elsevier Inc. All rights reserved.
引用
收藏
页码:128 / 133
页数:6
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