title: 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.
authors.affiliation: Division of Pharmacology, Dept. of Neuroscience and Reproductive and Odontostomatological Sciences, School of Medicine, "Federico II" University of Naples, Via Sergio Pansini 5, Naples, 80131, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Cocco
authors.affiliation: Division of Pharmacology, Dept. of Neuroscience and Reproductive and Odontostomatological Sciences, School of Medicine, "Federico II" University of Naples, Via Sergio Pansini 5, Naples, 80131, Italy.
authors.forename: Agnese
authors.initials: A
authors.lastname: Secondo
authors.affiliation: Dept. of Science and Technology-DST, University of Sannio, via Port'Arsa 11, 82100 Benevento, Italy.
authors.forename: Adelaide
authors.initials: A
authors.lastname: Del Viscovo
authors.affiliation: Laboratorio di Immunologia, Istituto di Endocrinologia e Oncologia Sperimentale, Consiglio Nazionale delle Ricerche (IEOS-CNR), c/o Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università di Napoli "Federico II", Napoli, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Procaccini
authors.affiliation: Dept. of Science and Technology-DST, University of Sannio, via Port'Arsa 11, 82100 Benevento, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Formisano
authors.affiliation: Division of Pharmacology, Dept. of Neuroscience and Reproductive and Odontostomatological Sciences, School of Medicine, "Federico II" University of Naples, Via Sergio Pansini 5, Naples, 80131, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Franco
authors.affiliation: Division of Pharmacology, Dept. of Neuroscience and Reproductive and Odontostomatological Sciences, School of Medicine, "Federico II" University of Naples, Via Sergio Pansini 5, Naples, 80131, Italy.
authors.forename: Alba
authors.initials: A
authors.lastname: Esposito
authors.affiliation: Division of Pharmacology, Dept. of Neuroscience and Reproductive and Odontostomatological Sciences, School of Medicine, "Federico II" University of Naples, Via Sergio Pansini 5, Naples, 80131, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Scorziello
authors.affiliation: Dipartimento di Medicina e Chirurgia, Università di Salerno, Baronissi Campus, Baronissi, Salerno, Italy; IRCCS MultiMedica, Milano, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Matarese
authors.affiliation: Division of Pharmacology, Dept. of Neuroscience and Reproductive and Odontostomatological Sciences, School of Medicine, "Federico II" University of Naples, Via Sergio Pansini 5, Naples, 80131, Italy.
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Di Renzo
authors.affiliation: Dept. of Science and Technology-DST, University of Sannio, via Port'Arsa 11, 82100 Benevento, Italy.
authors.forename: Lorella Maria Teresa
authors.initials: LM
authors.lastname: Canzoniero
mesh_terms: D000255:Adenosine Triphosphate / Q000096:biosynthesis; D045744:Cell Line, Tumor; D020111:Chlorodiphenyl (54% Chlorine) / Q000494:pharmacology*; D006019:Glycolysis; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D009447:Neuroblastoma / Q000378:metabolism / Q000473:pathology*; D009569:Nitric Oxide / Q000378:metabolism; D010085:Oxidative Phosphorylation; D019289:Pyruvic Acid / Q000494:pharmacology
chemical_list: D020111:Chlorodiphenyl (54% Chlorine); D009569:Nitric Oxide; D019289:Pyruvic Acid; D000255:Adenosine Triphosphate