探討氧化壓力下JNK途徑與細胞自噬系統之關係

Investigation of the relationship between JNK pathway and autophagy in response of oxidative stress.

廖筱嫚(Hsiao-man Liao)

指導教授 ： 陳光超

國立臺灣大學/生命科學院/生化科學研究所/碩士(2012年)

https://doi.org/10.6342/NTU.2012.10018

摘要

細胞自噬作用是真核生物演化上高度保留的途徑。其對於反應飢餓、缺氧與氧化壓力並且維持細胞內之平衡扮演著重要的角色。已有研究指出活性氧化物可以誘導細胞自噬作用。在本研究中，發現細胞長時間暴露於過氧化氫下，可以藉由活化JNK活性誘發細胞自噬作用。更進一步的，在細胞自噬系統被抑制的情形下，JNK的活性會被延長。由此結果可見，細胞自噬系統可以負向回饋調控氧化壓力下所活化之JNK活性。此外我們發現降低其中一個atg基因的表現量會抑制過氧化氫所活化的JNK活性。我們進一步發現這個Atg蛋白會與JNK途徑中的一員相互作用。總結，我們的研究證實在氧化壓力的環境下，此Atg蛋白可能做為JNK途徑與細胞自噬系統之間的連接。

關鍵字

細胞自噬系統 ； JNK途徑 ； Atg蛋白 ； 過氧化氫 ； 氧化壓力

並列摘要

Autophagy is a highly conserved pathway in eukaryotes. It plays a critical role in maintaining cellular homeostasis and in response to environmental stress, such as starvation, hypoxia and oxidative stress. It has been reported that ROS triggers autophagy. In our study, we found that long term H2O2 treatment induces autophagy via JNK-signaling pathway. Moreover, JNK activation was prolonged when autophagy was inhibited by 3-MA or depletion of atg genes, suggesting that autophagy may negative feedback regulate ROS-induced JNK activation. In addition, we found that the down regulation of one atg gene suppressed H2O2-induced JNK activity. We further showed that this Atg protein interacts with components of JNK pathway. In conclusion, our study provides evidence that Atg may act as a link between JNK signaling pathway and autophagy under oxidative stress conditions.

並列關鍵字

Autophagy ； JNK pathway ； Atg protein ； hydrogen peroxide ； oxidative stress

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