High-energy compounds mobilize intracellular Ca(2+) and activate calpain in cultured SH-SY5Y cells: potential use for preventing Alzheimer's disease.

High-energy compounds mobilize intracellular Ca(2+) and activate calpain in cultured SH-SY5Y cells: potential use for preventing Alzheimer's disease.
Brain Res Bull. 2014 Feb 4;
Authors: Nguyen HT, Chen M
Abstract
Deficiency in energy metabolisms is perhaps the earliest modifiable defect in brain aging and Alzheimer's disease (AD). Several high-energy compounds (HECs) such as ATP, phosphoenolpyruvate, phosphocreatine and acetyl coenzyme A have been shown to exhibit neuroprotective effects. To understand their mechanism of actions, we tested the effects of these HECs on intracellular Ca(2+), a central regulator in brain function. Our data showed that the HECs robustly and dose-dependently mobilized intracellular Ca(2+) in cultured SH-SY5Y cells, and the actions were sensitive to intracellular Ca(2+) chelator BAPTA-AM or energy metabolism blocker rotenone. The Ca(2+) influx triggered by the HECs was from both extracellular medium and intracellular stores and the HECs also induced repetitive Ca(2+) oscillations. As these actions were similar to those of classical Ca(2+) agonists, the HECs may be viewed as a new group of physiological Ca(2+) agonists. We also found that the HECs promoted the intracellular activity of calpain, a Ca(2+)-dependent protease, and the enzyme activity fluctuated in concert with cellular energy levels, suggesting that calpain activity may also be energy-driven or energy-dependent. These findings may add to current knowled...

Source: Brain Research Bulletin - February 4, 2014 Category: Neurology Authors: Nguyen HT, Chen M Tags: Brain Res Bull Source Type: research