Abstract
Arsenic is a common environmental pollutant that can cause damage to multiple systems and organs in the body. The lungs are particularly sensitive to arsenic exposure, and respiratory disease is thought to be the leading cause of death from arsenic poisoning. Our previous study found that human bronchial epithelial (HBE) cells treated with NaAsO2 exhibited mitochondrial dysfunction accompanied by elevated HIF-1α; however, the molecular mechanism was unclear. The aim of the current study was to confirm the role of HIF-1α in arsenic-induced mitochondrial damage. The results of this study indicated that NaAsO2 treatment induced mitochondrial ultrastructure impairment and depolarization of the mitochondrial membrane potential. Furthermore, NaAsO2 induced a significant decrease in basal respiration, maximal respiration, spare respiratory capacity, ATP (adenosine-triphosphate)-associated mitochondrial respiration and proton leakage in HBE cells (P < 0.05), while promoting an increase in ECAR (extracellular acidification rate) values. To clarify the role of HIF-1α, the effect of HIF-1α siRNA on NaAsO2-induced glycolysis in HBE cells was examined, and the results showed that HIF-1α siRNA reversed the NaAsO2-induced elevation in PKM2 (Tyr105), HIF-1α, GLUT1 and HK2 protein expression and decreased the NaAsO2-mediated glycolysis level, glycolytic capacity and glycolytic reserve. These findings suggest that targeting metabolic dysregulation has significant implications for targeting arsenic-induced lung injury and that HIF-1α is an exciting new therapeutic target for the treatment of arsenic-induced lung injury.