Tellurium/Bovine Serum Albumin Nanocomposites Inducing the Formation of Stress Granules in a Protein Kinase R-Dependent Manner.

ABSTRACT

The effect of nanoparticles (NPs) on cellular stress responses is important to the understanding of nanotoxicities and developing safe therapies. Although the relationship between NPs and cellular stress responses has been preliminarily investigated, stress responses to NPs remain unclear. Here, tellurium/bovine serum albumin (Te/BSA) nanocomposites were prepared using sodium tellurite, BSA, and glutathione as precursors. The as-prepared Te/BSA nanocomposites, with particle size similar to that of many viruses, are found to induce the formation of stress granules (SGs), a kind of cytoplasmic RNA granule formed under various stresses. The SGs in Te/BSA nanocomposite-treated cells are composed of T-cell internal antigen 1 (TIA1), TIA1-related protein, and eukaryotic initiation factor 3η. Using chemical inhibitors and small interfering RNA-mediated silencing, protein kinase R (PKR) is identified as the α-subunit of eukaryotic initiation factor 2 (eIF2α)-kinase activated upon Te/BSA nanocomposite incubation, which is also the dominant kinase responsible for eIF2α activation under virus infection. Mechanistically, PKR is activated in a heparin-dependent manner. This study reveals a biological effect of Te/BSA nanocomposites on stress responses, providing a preliminary basis for further research on viruslike particles and the application of NPs in biology.