title: Aroclor 1254, a developmental neurotoxicant, alters energy metabolism- and intracellular signaling-associated protein networks in rat cerebellum and hippocampus.
abstract: The vast literature on the mode of action of polychlorinated biphenyls (PCBs) indicates that PCBs are a unique model for understanding the mechanisms of toxicity of environmental mixtures of persistent chemicals. PCBs have been shown to adversely affect psychomotor function and learning and memory in humans. Although the molecular mechanisms for PCB effects are unclear, several studies indicate that the disruption of Ca(2+)-mediated signal transduction plays significant roles in PCB-induced developmental neurotoxicity. Culminating events in signal transduction pathways include the regulation of gene and protein expression, which affects the growth and function of the nervous system. Our previous studies showed changes in gene expression related to signal transduction and neuronal growth. In this study, protein expression following developmental exposure to PCB is examined. Pregnant rats (Long Evans) were dosed with 0.0 or 6.0mg/kg/day of Aroclor-1254 from gestation day 6 through postnatal day (PND) 21, and the cerebellum and hippocampus from PND14 animals were analyzed to determine Aroclor 1254-induced differential protein expression. Two proteins were found to be differentially expressed in the cerebellum following PCB exposure while 18 proteins were differentially expressed in the hippocampus. These proteins are related to energy metabolism in mitochondria (ATP synthase, sub unit β (ATP5B), creatine kinase, and malate dehydrogenase), calcium signaling (voltage-dependent anion-selective channel protein 1 (VDAC1) and ryanodine receptor type II (RyR2)), and growth of the nervous system (dihydropyrimidinase-related protein 4 (DPYSL4), valosin-containing protein (VCP)). Results suggest that Aroclor 1254-like persistent chemicals may alter energy metabolism and intracellular signaling, which might result in developmental neurotoxicity.
authors.affiliation: Neurotoxicology Branch, NHEERL, ORD, US Environmental Protection Agency, Research Triangle Park, North Carolina 27711, USA. kodavanti.prasada@epa.gov
authors.forename: Prasada Rao S
authors.initials: PR
authors.lastname: Kodavanti
authors.forename: Cristina
authors.initials: C
authors.lastname: Osorio
authors.forename: Joyce E
authors.initials: JE
authors.lastname: Royland
authors.forename: Ram
authors.initials: R
authors.lastname: Ramabhadran
authors.forename: Oscar
authors.initials: O
authors.lastname: Alzate
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002531:Cerebellum / Q000166:cytology / Q000187:drug effects*; D020111:Chlorodiphenyl (54% Chlorine) / Q000494:pharmacology / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D015180:Electrophoresis, Gel, Two-Dimensional; D004734:Energy Metabolism / Q000187:drug effects*; D005260:Female; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects*; D008928:Mitochondria / Q000187:drug effects; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000187:drug effects; D020258:Neurotoxicity Syndromes / Q000209:etiology / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced; D040901:Proteomics; D051381:Rats; D020318:Rats, Long-Evans; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D009419:Nerve Tissue Proteins; D020111:Chlorodiphenyl (54% Chlorine)