Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Arsenic-Induced Mitochondria-Mediated Apoptosis is Associated with PGC-1α Decrease in Rat Brain

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These authors contributed equally to the work and should be considered as first authors
These authors contributed equally to the work and should be considered as corresponding authors
Version 1 : Received: 25 May 2023 / Approved: 26 May 2023 / Online: 26 May 2023 (10:21:09 CEST)

A peer-reviewed article of this Preprint also exists.

Ding, B.; Ma, X.; Liu, Y.; Ni, B.; Lu, S.; Chen, Y.; Liu, X.; Zhang, W. Arsenic-Induced, Mitochondria-Mediated Apoptosis Is Associated with Decreased Peroxisome Proliferator-Activated Receptor γ Coactivator α in Rat Brains. Toxics 2023, 11, 576. Ding, B.; Ma, X.; Liu, Y.; Ni, B.; Lu, S.; Chen, Y.; Liu, X.; Zhang, W. Arsenic-Induced, Mitochondria-Mediated Apoptosis Is Associated with Decreased Peroxisome Proliferator-Activated Receptor γ Coactivator α in Rat Brains. Toxics 2023, 11, 576.

Abstract

Chronic exposure to arsenic in drinking-water damage to cognitive function, and nerve cells apoptosis is one of primary characteristic. The damage of 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 role of PGC-1α in sodium arsenite (NaAsO2)-induced mitochondrial apoptosis in rat hippocampal cells. We discovered that arsenic-induced apoptosis increased 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, swollen, lysosomes and lipofuscin increasing, and nuclear membrane shrunk observed by transmission electron microscope. Furthermore, NaAsO2 reduced levels of Bcl-2 and PGC-1α, increased the levels of Bax and Cytochrome C expression. Moreover, correlation analysis showed that brain arsenic content was negatively correlated with PGC-1α level and brain ATP content, respectively; PGC-1α level was negatively correlated with apoptosis rate; Brain ATP content was positively correlated with PGC-1α level; but no significant correlation between ATP content and apoptosis has been observed in this study. Taken together, the results of present study indicate that NaAsO2-induced mitochondrial pathway apoptosis is related to the reduction of PGC-1α, accompanied by ATP depletion.

Keywords

Arsenic, PGC-1α, Mitochondria, Hippocampus, Apoptosis

Subject

Public Health and Healthcare, Public, Environmental and Occupational Health

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