Chapter 12 - Endoplasmic reticulum stress-induced cell death mechanism

Abstract

Exposure to nanoparticles (NPs) may modulate endoplasmic reticulum (ER) stress, which could be a target for future nanotoxicological and nonmedicinal studies. The ER is a crucial organelle involved in proper protein folding. High levels of misfolded proteins in the ER could lead to a condition called ER stress, which may ultimately influence the fate of cells and development of human diseases. In this chapter, we summarize studies on the effects of NP exposure on ER stress. A variety of NPs, especially metal-based NPs, could induce morphological changes of the ER and activate the ER stress pathway both in vivo and in vitro. In addition, modulation of ER stress by chemicals has been shown to alter the toxicity of NPs. These studies in combination suggest that ER stress could be the mechanism responsible for NP-induced toxicity. Understanding the mechanism of NP-induced ER stress cell death toxicity is important for nanotoxicological and nonmedicinal studies. Meanwhile, nonmedicinal studies also use ER stress-inducing NPs or NPs loaded with an ER stress inducer to selectively induce ER stress-mediated apoptosis in cancer cells for cancer therapy. In contrast, alleviation of ER stress by NPs has also been shown as a strategy to cure metabolic diseases. In summary, preliminary assessment of NP-induced toxicity by monitoring the ER stress-signaling pathway provides novel assumptions toward empathizing the effects of NPs at the cellular level. The adverse effects associated with exposure to NPs can be avoided by sensibly using these minerals within safe doses.