Identification of the Nanogold Particle-Induced Endoplasmic Reticulum Stress by Omic Techniques and Systems Biology Analysis

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• 作者：Yen-Yin Tsai ; Yi-Huei Huang ; Ya-Li Chao ; Kuang-Yu Hu ; Li-Te Chin ; Shiu-Huey Chou ; Ai-Ling Hour ; Yeong-Der Yao ; Chi-Shun Tu ; Yao-Jen Liang ; Cheng-Yuh Tsai ; Hao-Yu Wu ; Shan-Wen Tan ; Han-Min Chen
• 刊名：ACS Nano
• 出版年：2011
• 出版时间：December 27, 2011
• 年：2011
• 卷：5
• 期：12
• 页码：9354-9369
• 全文大小：1479K
• 年卷期：0
• ISSN：1936-086X

文摘

Growth inhibition and apoptotic/necrotic phenotype was observed in nanogold particle (AuNP)-treated human chronic myelogenous leukemia cells. To elucidate the underlying cellular mechanisms, proteomic techniques including two-dimensional electrophoresis/mass spectrometry and protein microarrays were utilized to study the differentially expressed proteome and phosphoproteome, respectively. Systems biology analysis of the proteomic data revealed that unfolded protein-associated endoplasmic reticulum (ER) stress response was the predominant event. Concomitant with transcriptomic analysis using mRNA expression, microarrays show ER stress response in the AuNP-treated cells. The ER stress protein markers’ expression assay unveiled AuNPs as an efficient cellular ER stress elicitor. Upon ER stress, cellular responses, including reactive oxygen species increase, mitochondrial cytochrome c release, and mitochondria damage, chronologically occurred in the AuNP-treated cells. Conclusively, this study demonstrates that AuNPs cause cell death through induction of unmanageable ER stress.