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CHANGES IN PROTEOMIC PROFILES OF CEREBELLUM FOLLOWING DEVELOPMENTAL EXPOSURE TO AROCLOR 1254 OR DE-71.
Citation:
KODAVANTI, PRASADA RAO S., J. E. ROYLAND, T. V. RAMABHADRAN, C. OSORIO, AND O. ALZATE. CHANGES IN PROTEOMIC PROFILES OF CEREBELLUM FOLLOWING DEVELOPMENTAL EXPOSURE TO AROCLOR 1254 OR DE-71. Presented at 27th Int'l Symposium on Halogenated Environmental Organic Pollutants and POPs, Tokyo, JAPAN, September 03 - 07, 2007.
Description:
Chronic low level exposure to polychlorinated biphenyls (PCBs) has been shown to adversely affect human health, including learning and memory. Polybromiated diphenyl ethers (PBDEs) are structurally similar to PCBs and have been shown to have neurotoxic effects in vitro and in vivo at concentrations/doses similar to those of PCBs. Although the cellular and molecular bases for these actions is not fully understood, several studies have shown that in addition to their effects on thyroid hormones, disruption of Ca2+-mediated signal transduction plays a significant role in the developmental neurotoxicity of these persistent chemicals. Changes in a variety of signal transduction pathways can lead to gene regulation and protein expression, which affect the growth and function of the nervous system. Our previous studies on PCBs showed changes in gene expression profiles related to signal transduction and neuronal growth. In this study, we have examined the protein expression profiles in cerebellum following developmental exposure to Aroclor 1254 (a commercial PCB mixture) or DE-71 (a commercial PBDE mixture). Pregnant rats (Long Evans) were dosed perinatally with 0.6 mg/kg/day of Aroclor 1254 or 30.2 mg/kg/day of DE-71 from gestation day 6 through postnatal day (PND) 21, and the cerebellum from PND14 animals were analyzed. Proteins differentially expressed following PCB or PBDE exposure were detected by two-dimensional differential gel electrophoresis (2D-DIGE) using fluorescent cyanine dye labeling and identified by tandem mass spectrometry (MS). Two proteins were found to be differentially expressed in the cerebellum following PCB exposure and four were differentially expressed following DE-71 exposure. Protein identification revealed that these proteins are related to mitochondrial energy metabolism, calcium signaling, and growth of the nervous system. These results suggest that changes in energy metabolism and intracellular signaling may be involved in the developmental neurotoxicity of persistent chemicals.