Javan Gulnaz T, Kwon Insu, Finley Sheree J, Lee Youngil
Forensic Science Program, Physical Sciences Department, Alabama State University, Montgomery, AL, United States.
Department of Exercise Science and Community Health, University of West Florida, Pensacola, FL, United States.
Biochem Biophys Rep. 2015 Nov 18;5:152-159. doi: 10.1016/j.bbrep.2015.11.013. eCollection 2016 Mar.
Autophagy is an evolutionarily conserved catabolic process for maintaining cellular homeostasis during both normal and stress conditions. Metabolic reprogramming in tissues of dead bodies is inevitable due to chronic ischemia and nutrient deprivation, which are well-known features that stimulate autophagy. Currently, it is not fully elucidated whether postmortem autophagy, also known as thanatophagy, occurs in dead bodies is a function of the time of death. In this study, we tested the hypothesis that thanatophagy would increase in proportion to time elapsed since death for tissues collected from cadavers. Brain and heart tissue from corpses at different time intervals after death were analyzed by Western blot. Densitometry analysis demonstrated that thanatophagy occurred in a manner that was dependent on the time of death. The autophagy-associated proteins, LC3 II, p62, Beclin-1 and Atg7, increased in a time-dependent manner in heart tissues. A potent inducer of autophagy, BNIP3, decreased in the heart tissues as time of death increased, whereas the protein levels increased in brain tissues. However, there was no expression of BNIP3 at extended postmortem intervals in both brain and heart samples. Collectively, the present study demonstrates for the first time that thanatophagy occurs in brain and heart tissues of cadavers in a time-dependent manner. Further, our data suggest that cerebral thanatophagy may occur in a Beclin-1- independent manner. This unprecedented study provides potential insight into thanatophagy as a novel method for the estimation of the time of death in criminal investigationsAbstract: Autophagy is an evolutionarily conserved catabolic process for maintaining cellular homeostasis during both normal and stress conditions. Metabolic reprogramming in tissues of dead bodies is inevitable due to chronic ischemia and nutrient deprivation, which are well-known features that stimulate autophagy. Currently, it is not fully elucidated whether postmortem autophagy, also known as thanatophagy, occurs in dead bodies is a function of the time of death. In this study, we tested the hypothesis that thanatophagy would increase in proportion to time elapsed since death for tissues collected from cadavers. Brain and heart tissue from corpses at different time intervals after death were analyzed by Western blot. Densitometry analysis demonstrated that thanatophagy occurred in a manner that was dependent on the time of death. The autophagy-associated proteins, LC3 II, p62, Beclin-1 and Atg7, increased in a time-dependent manner in heart tissues. A potent inducer of autophagy, BNIP3, decreased in the heart tissues as time of death increased, whereas the protein levels increased in brain tissues. However, there was no expression of BNIP3 at extended postmortem intervals in both brain and heart samples. Collectively, the present study demonstrates for the first time that thanatophagy occurs in brain and heart tissues of cadavers in a time-dependent manner. Further, our data suggest that cerebral thanatophagy may occur in a Beclin-1- independent manner. This unprecedented study provides potential insight into thanatophagy as a novel method for the estimation of the time of death in criminal investigations.
自噬是一种在正常和应激条件下维持细胞内稳态的进化保守分解代谢过程。由于慢性缺血和营养剥夺，尸体组织中的代谢重编程不可避免，而慢性缺血和营养剥夺是刺激自噬的众所周知的特征。目前，尚不完全清楚死后自噬（也称为死亡自噬）是否在尸体中发生以及是否是死亡时间的函数。在本研究中，我们测试了这样一个假设：对于从尸体采集的组织，死亡自噬会随着死亡时间的延长而成比例增加。通过蛋白质免疫印迹法分析了死后不同时间间隔尸体的脑和心脏组织。光密度分析表明，死亡自噬以依赖于死亡时间的方式发生。自噬相关蛋白LC3 II、p62、Beclin-1和Atg7在心脏组织中呈时间依赖性增加。自噬的强效诱导剂BNIP3在心脏组织中随着死亡时间的增加而减少，而在脑组织中蛋白质水平增加。然而，在脑和心脏样本中延长的死后间隔时间均未检测到BNIP3的表达。总的来说，本研究首次证明死亡自噬以时间依赖性方式发生在尸体的脑和心脏组织中。此外，我们的数据表明，脑死亡自噬可能以不依赖Beclin-1的方式发生。这项前所未有的研究为死亡自噬作为刑事调查中估计死亡时间的一种新方法提供了潜在的见解。摘要：自噬是一种在正常和应激条件下维持细胞内稳态的进化保守分解代谢过程。由于慢性缺血和营养剥夺，尸体组织中的代谢重编程不可避免，而慢性缺血和营养剥夺是刺激自噬的众所周知的特征。目前，尚不完全清楚死后自噬（也称为死亡自噬）是否在尸体中发生以及是否是死亡时间的函数。在本研究中，我们测试了这样一个假设：对于从尸体采集的组织，死亡自噬会随着死亡时间的延长而成比例增加。通过蛋白质免疫印迹法分析了死后不同时间间隔尸体的脑和心脏组织。光密度分析表明，死亡自噬以依赖于死亡时间的方式发生。自噬相关蛋白LC3 II、p62、Beclin-1和Atg7在心脏组织中呈时间依赖性增加。自噬的强效诱导剂BNIP3在心脏组织中随着死亡时间的增加而减少，而在脑组织中蛋白质水平增加。然而，在脑和心脏样本中延长的死后间隔时间均未检测到BNIP3的表达。总的来说，本研究首次证明死亡自噬以时间依赖性方式发生在尸体的脑和心脏组织中。此外，我们的数据表明，脑死亡自噬可能以不依赖Beclin-1的方式发生。这项前所未有的研究为死亡自噬作为刑事调查中估计死亡时间的一种新方法提供了潜在的见解。
