Hepatic autophagy after severe burn in response to endoplasmic reticulum stress.
Hepatic autophagy after severe burn in response to endoplasmic reticulum stress.
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DOI：
10.1016/j.jss.2013.09.042
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发表时间：
2014-03
影响因子：
2.2
通讯作者：
Wolf, Steven E.
中科院分区：
文献类型：
--
作者：
Song, Juquan;de Libero, Jana;Wolf, Steven E.
先前的研究显示严重烧伤后肝功能障碍，这与内质网应激的激活有关。自噬是维持细胞器平衡的分解代谢过程；内质网应激与自噬信号级联反应有关。因此，我们试图确定自噬信号是否与烧伤后肝脏损伤相关，以及烧伤相关内质网应激是否激活肝细胞中的自噬信号。C57BL6雄性小鼠给予25%体表面积全厚度（TBSA）烫伤，烫伤后24小时取肝。用内质网应激诱导剂thapsigarin （TG）刺激HepG2细胞24小时，模拟体外内质网应激。肝组织切片行TUNEL染色。免疫印迹法检测自噬情况。统计学分析采用Student’s t检验，p<0.05为显著性。烧伤动物TUNEL阳性染色的肝细胞增多，caspase - 3活性显著升高（p<0.05）。肝脏ATG3、ATG5、LC3B均显著升高（p<0.05）。HepG2细胞对TG的反应中Beclin-1、LC3A和LC3B的表达增加，与体内反应相似。甘油三酯显著降低了细胞内ATP， AMPK和mTOR磷酸化（p<0.05）。内质网应激发生在严重损伤后的肝细胞中，与严重烧伤后的自噬和肝损伤有关。在内质网应激下，活化的自噬与AMPK/mTOR通路有关。
Previous studies showed liver dysfunction after severe burn, and that 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. C57BL6 male mice received a 25% total body surface area full thickness (TBSA) scald burn, and liver was harvested at 24 hours after burn. HepG2 cells were stimulated with an ER stress inducer thapsigargin (TG) for 24 hours to mimic ER stress in vitro. TUNEL staining was performed on liver histology sections. Autophagy was assessed by immunoblotting. Statistical analysis was by Student’s t-test and significance was accepted at p<0.05. TUNEL positive stained hepatocytes increased in burned animals with a significant elevation of caspase 3 activity (p<0.05). A marked increase in hepatic ATG3, ATG5 and LC3B was detected as well (p<0.05). Expression of Beclin-1, LC3A and LC3B increased in HepG2 cells in response to TG, similar to the response seen in vivo. Cytosolic ATP dropped significantly, and AMPK and mTOR were phosphorylated as well in response to TG (p<0.05). ER stress, which occurs in hepatocytes after severe injury, is associated with autophagy and liver damage following severe burn. In response to ER stress, activated autophagy is associated with AMPK/mTOR pathway.
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影响因子：
11.1
作者：
He C;Klionsky DJ
通讯作者：
Klionsky DJ
影响因子：
21.3
作者：
通讯作者：
--
影响因子：
4.8
作者：
Noda, T;Ohsumi, Y
通讯作者：
Ohsumi, Y
影响因子：
3.7
作者：
Jeschke MG;Gauglitz GG;Kulp GA;Finnerty CC;Williams FN;Kraft R;Suman OE;Mlcak RP;Herndon DN
通讯作者：
Herndon DN
影响因子：
13.3
作者：
Wu, You-Tong;Tan, Hui-Ling;Shen, Han-Ming
通讯作者：
Shen, Han-Ming