Metabolic Stress and Mitochondrial Dysfunction in Ataxia-Telangiectasia.

The ataxia-telangiectasia mutated (ATM) protein kinase is, as the name implies, mutated in the human genetic disorder ataxia-telangiectasia (A-T). This protein has its "finger in many pies", being responsible for the phosphorylation of many thousands of proteins in different signaling pathways in its role in protecting the cell against a variety of different forms of stress that threaten to perturb cellular homeostasis. The classical role of ATM is the protection against DNA damage, but it is evident that it also plays a key role in maintaining cell homeostasis in the face of oxidative and other forms of non-DNA damaging stress. The presence of ATM is not only in the nucleus to cope with damage to DNA, but also in association with other organelles in the cytoplasm, which suggests a greater protective role. This review attempts to address this greater role of ATM in protecting the cell against both external and endogenous damage.

Mechanism of cell death induced by silica nanoparticles in hepatocyte cells is by apoptosis.

Silicon is one of the most widely used chemical materials, and the increasing use of silica nanoparticles (SNs) highlights the requirement for safety and biological toxicity studies. The damaging and adverse effects of SNs on human hepatocytes remain largely unknown, as do the mechanisms involved. In the present study, the mechanisms underlying SN­induced toxicity in the human hepatocyte cell line HL­7702 were investigated. An MTT assay revealed that following exposure to SNs in the concentration range of 25­200 µg/ml, the viability of HL­7702 cells decreased, and the viability decreased further with increasing exposure time. SNs induced a delay in the S and G2/M phases of the cell cycle, and also induced DNA damage in these cells. Western blot and flow cytometry analyses revealed that cell death was mediated by mitochondrial damage and the upregulated expression of a number of pro­apoptotic proteins. In conclusion, exposure to SNs led to mitochondrial and DNA damage, resulting in apoptosis­mediated HL­7702 cell death. The study provided evidence for the cellular toxicity of SNs, and added to the growing body of evidence regarding the potential damaging effects of nanoparticles, indicating that caution should be exercised in their widespread usage.