Polychlorinated Biphenyls Induce Mitochondrial Dysfunction in SH-SY5Y Neuroblastoma Cells

Abstract

Chronic exposure to polychlorinated biphenyls (PCBs), ubiquitous environmental contaminants, can adversely affect the development and function of the nervous system. Here we evaluated the effect of PCB exposure on mitochondrial function using the PCB mixture Aroclor-1254 (A1254) in SH-SY5Y neuroblastoma cells. A 6-hour exposure to A1254 (5 μg/ml) reduced cellular ATP production by 45%±7, and mitochondrial membrane potential, detected by TMRE, by 49%±7. Consistently, A1254 significantly decreased oxidative phosphorylation and aerobic glycolysis measured by extracellular flux analyzer. Furthermore, the activity of mitochondrial protein complexes I, II, and IV, but not V (ATPase), measured by BN-PAGE technique, was significantly reduced after 6-hour exposure to A1254. The addition of pyruvic acid during exposure to A1254 significantly prevent A1254-induced cell injury, restoring resting mitochondrial membrane potential, ATP levels, oxidative phosphorylation and aerobic glycolysis. Furthermore, pyruvic acid significantly preserved the activity of mitochondrial complexes I, II and IV and increased basal activity of complex V. Collectively, the present results indicate that the neurotoxicity of A1254 depends on the impairment of oxidative phosphorylation, aerobic glycolysis, and mitochondrial complexes I, II, and IV activity and it was counteracted by pyruvic acid.

Nrf2 activation through the PI3K/GSK-3 axis protects neuronal cells from Aβ-mediated oxidative and metabolic damage

“…As a result, FCCP uncouples respiration from ATP synthesis allowing determination of the maximal respiratory capacity of the electron transport chain only limited by substrate supply. In our system, FCCP completely restored basal respiration levels in SH-SY5Y cells and increased OCR values in~60% in DIV7 neurons, consistent with previous findings [39,40]. The difference in the FCCP response between SH-SY5Y and primary neurons likely reflects neuronal differentiation, as it has been reported that while maximal respiration did not increase above basal levels in nondifferentiated cells, FCCP-induced OCR values were significantly higher in differentiated neurons [39].…”

Chlorinated biphenyls effect on estrogen-related receptor expression, steroid secretion, mitochondria ultrastructure but not on mitochondrial membrane potential in Leydig cells

“…In rat brain in vitro, PCBs inhibited mitochondrial Ca2+ uptake (Kodavanti and Ward 2005 ), while in brain and liver cells of rats, significant reductions of oxygen consumption and respiratory chain complexes II and III have been demonstrated (Ounnas et al 2016 ). In addition, induction of mitochondria dysfunction by PCBs in SH-SY5Y (neuroblastoma cells) and Vero cells (kidney epithelial cell line) was recently shown by Shen et al ( 2011 ) and Cocco et al ( 2015 ). In the present study, we reported modulation of ERRs expression and function as well as ultrastructure of mitochondria in Leydig cells treated with PCBs.…”

Telomerase gene expression bioassays indicate metabolic activation of genotoxic lower chlorinated polychlorinated biphenyls

“…PCBs have been shown to induce mitochondrial dysfunction and oxidative stress in vitro 40 and upon application in vivo , reduce the surfaces and volume density of mitochondria while maintaining their numbers at a constant rate. As a consequence, the energy supply of mitochondria were reduced, as could be demonstrated by incubating Jurkat T cells with OH-PCBs at a concentration of 500 nM (Fig.…”