Arsenic-Induced, Mitochondria-Mediated Apoptosis Is Associated with Decreased Peroxisome Proliferator-Activated Receptor γ Coactivator α in Rat Brains

Abstract

Chronic exposure to arsenic in drinking water damages cognitive function, and nerve cell apoptosis is one of the primary characteristics. The damage to mitochondrial structure and/or function is one of the main characteristics of apoptosis. Peroxisome proliferator-activated receptor γ coactivator α (PGC-1α) is involved in the regulation of mitochondrial biogenesis, energy metabolism, and apoptosis. In this study, we aimed to study the role of PGC-1α in sodium arsenite (NaAsO2)-induced mitochondrial apoptosis in rat hippocampal cells. We discovered that increased arsenic-induced apoptosis in rat hippocampus increased with NaAsO2 (0, 2, 10, and 50 mg/L, orally via drinking water for 12 weeks) exposure by TUNEL assay, and the structure of mitochondria was incomplete and swollen and had increased lysosomes, lipofuscins, and nuclear membrane shrinkage observed via transmission electron microscopy. Furthermore, NaAsO2 reduced the levels of Bcl-2 and PGC-1α and increased the levels of Bax and cytochrome C expression. Moreover, correlation analysis showed that brain arsenic content was negatively correlated with PGC-1α levels and brain ATP content; PGC-1α levels were negatively correlated with apoptosis rate; and brain ATP content was positively correlated with PGC-1α levels, but no significant correlation between ATP content and apoptosis has been observed in this study. Taken together, the results of this study indicate that NaAsO2-induced mitochondrial pathway apoptosis is related to the reduction of PGC-1α, accompanied by ATP depletion.