Role of Endoplasmic Reticulum ER Stress-Induced Cell Death Mechanisms

Abstract

Understanding the mechanism of nanoparticle (NP)-induced toxicity is important for nanotoxicological and nanomedicinal studies. Endoplasmic reticulum (ER) is a crucial organelle involved in proper protein folding. High levels of misfolded proteins in the ER could lead to a condition termed as ER stress, which may ultimately influence the fate of cells and the development of human diseases. In this review, we summarized studies about effects of NP exposure on ER stress. A variety of NPs, especially metal-based NPs, could induce morphological changes of ER and activate 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 suggested that ER stress could be the mechanism responsible for NP-induced toxicity. Meanwhile, nanomedicinal studies also used ER stress-inducing NPs or NPs loaded with ER stress inducer to selectively induce ER stress-mediated apoptosis in cancer cells for cancer therapy. In contrast, the alleviation of ER stress by NPs has also been shown as a strategy to cure metabolic diseases. In summary, the preliminary assessment of NPs-induced toxicity by monitoring the ER stress-signaling pathway gives novel assumptions toward empathizing the effects of NPs at the cellular level. The adverse effects associated with the exposure to NPs can be avoided by sensibly using these minerals within the safe dose. In conclusion, exposure to NPs may modulate ER stress, which could be a target for future nanotoxicological and nanomedicinal studies.