4.8 Article

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

Journal

ACS NANO
Volume 5, Issue 12, Pages 9354-9369

Publisher

AMER CHEMICAL SOC
DOI: 10.1021/nn2027775

Keywords

nanogold particles; proteomics; transcriptomics; systems biology; endoplasmic reticulum stress

Funding

  1. Gold Nanotech, Inc.
  2. Catholic Fu-Jen University [099630110, 109931041001-2]

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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.

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