title: Effects of subchronic perfluorooctane sulfonate exposure of rats on calcium-dependent signaling molecules in the brain tissue.
abstract: Perfluorooctane sulfonate (PFOS) is a persistent and bio-accumulative pollutant ubiquitous in wildlife and humans, which receives many concerns on the fate, transport, distribution, and toxicity. Studies have shown that PFOS-induced neurotoxicity in experimental animals; however, little is known about the potential mechanism of PFOS exposure on the central nervous system (CNS). Ca(2+)/calmodulin-dependent protein kinase IIalpha (CaMKIIalpha), cAMP-response element binding protein (CREB), c-fos, and c-jun, which are important down-stream molecules of calcium signaling in describing neuron cells structure and function in the CNS, were examined in the paper with the purpose to evaluate the effect of PFOS exposure on brain and approach the molecular mechanisms involved in the neurotoxicity induced by PFOS. Adult male Sprague-Dawley rats were administered with PFOS at dosages of 1.7, 5.0, and 15.0 mg/L in drinking water for 91 consecutive days. LC/MS was used for PFOS analysis in brain tissues, and western blot was employed to determine the expression of CaMKIIalpha and pCREB in the isolated cortex and hippocampus. The expression of c-fos and c-jun was detected by real-time reverse transcription polymerase chain reaction. The results showed that the expression of CaMKIIalpha and pCREB exhibits a significant increase in cortex and hippocampus after treatment with PFOS, compared with the control. The transcription factor c-fos was up-regulated in hippocampus, and c-jun was elevated both in cortex and hippocampus in PFOS-treated groups. These results indicated that, at least in part, the neurotoxic effect induced by PFOS is mediated by the Ca(2+)-dependent molecules in calcium signaling.
authors.affiliation: School of Environmental and Biological Science and Technology, Key Laboratory of Industrial Ecology and Environmental Engineering, Ministry of Education, Dalian University of Technology, Linggong Road 2, 116024, Dalian, China.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Liu
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.forename: Yihe
authors.initials: Y
authors.lastname: Jin
authors.forename: Wenguang
authors.initials: W
authors.lastname: Yu
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.forename: Hongyao
authors.initials: H
authors.lastname: Yu
mesh_terms: D000284:Administration, Oral; D017738:Alkanesulfonic Acids / Q000493:pharmacokinetics / Q000633:toxicity*; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D050882:CREB-Binding Protein / Q000235:genetics / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000235:genetics / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D004785:Environmental Pollutants / Q000493:pharmacokinetics / Q000633:toxicity*; D005466:Fluorocarbons / Q000493:pharmacokinetics / Q000633:toxicity*; D015870:Gene Expression / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D021241:Spectrometry, Mass, Electrospray Ionization; D018675:Toxicity Tests
chemical_list: D017738:Alkanesulfonic Acids; D004785:Environmental Pollutants; D005466:Fluorocarbons; C076994:perfluorooctane sulfonic acid; D050882:CREB-Binding Protein; C494365:Crebbp protein, rat; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; C517675:Camk2a protein, rat; D002118:Calcium