Dadakhujaev Shorafidinkhuja, Jung Eun Joo, Noh Hae Sook, Hah Young-Sool, Kim Chang Jae, Kim Deok Ryong
Department of Biochemistry and MRCND and Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju, Republic of Korea.
Autophagy. 2009 Jan;5(1):103-5. doi: 10.4161/auto.5.1.7276.
Autophagy is a self-eating process to eradicate damaged proteins or organelles in cells. This process begins with formation of a double-membrane structure, called an autophagosome, which can sequester soluble proteins and organelles eventually degraded by lysosomal proteases after fusion with the lysosome. Autophagy was initially identified as a cell survival mechanism under stress conditions such as nutrient deprivation. More recently, it is also considered as type-II programmed cell death. In our recent report, we observed that overexpression of TrkA caused massive cell death via both apoptosis and autophagy. Overexpression of TrkA abated catalase activity and subsequently resulted in the production of a large amount of reactive oxygen species in cells. These consequences led to autophagic cell death. The autophagic cell death in TrkA-overexpressing cells was validated by GFP-LC3 dot formation, production of autophagosomes or acidic vacuoles, LC3 lipidation, and depletion of autopahgy-related genes. In addition, we also observed some evidence for apoptosis in TrkA-expressing cells. Many cells expressing TrkA exhibited annexin V-positive staining, activation of caspase-7 and BAX. Moreover, TrkA activated the JNK pathway, leading to phosphorylation of H2AX. In this report, we suggest that two cell death mechanisms occur simultaneously and interlink with each other. The JNK-calpain pathway might be a central process to mediate the two processes in TrkA-overexpressing cells, although further study still remains to prove the interplay between autophagy and apoptosis.
自噬是一种细胞自我吞噬的过程，用于清除细胞内受损的蛋白质或细胞器。这个过程始于一种称为自噬体的双膜结构的形成，自噬体能够隔离可溶性蛋白质和细胞器，最终在与溶酶体融合后被溶酶体蛋白酶降解。自噬最初被认为是在营养剥夺等应激条件下的一种细胞存活机制。最近，它也被视为II型程序性细胞死亡。在我们最近的报告中，我们观察到TrkA的过表达通过凋亡和自噬导致大量细胞死亡。TrkA的过表达降低了过氧化氢酶的活性，随后导致细胞内产生大量活性氧。这些结果导致了自噬性细胞死亡。通过GFP-LC3斑点形成、自噬体或酸性液泡的产生、LC3脂化以及自噬相关基因的缺失，证实了TrkA过表达细胞中的自噬性细胞死亡。此外，我们还观察到一些TrkA表达细胞中凋亡的证据。许多表达TrkA的细胞表现出膜联蛋白V阳性染色、半胱天冬酶-7和BAX的激活。此外，TrkA激活了JNK途径，导致H2AX磷酸化。在本报告中，我们认为两种细胞死亡机制同时发生并相互关联。JNK-钙蛋白酶途径可能是介导TrkA过表达细胞中这两个过程的核心过程，尽管仍需进一步研究来证明自噬和凋亡之间的相互作用。
