title: Perfluorooctane sulfonate-induced apoptosis of cerebellar granule cells is mediated by ERK 1/2 pathway.
abstract: Perfluorooctane sulfonate (PFOS), a ubiquitous environmental pollutant, is considered as a neurotoxicant to mammalian species. However, the underlying mechanism of its neurotoxicity is largely unknown. In the present study, we examined roles of mitogen-activated protein kinases (MAPKs) in PFOS-induced apoptosis of neuronal cells to elucidate the molecular mechanism. Cerebellar granule cells were isolated from 7-d old rats and maintained in culture for additional 7 d. Cells were exposed to PFOS and caspase-3 activity and nuclear morphology were evaluated by enzyme activity assay and Hoechst 33342 staining, respectively, to determine its effects on apoptosis. The treatment with PFOS resulted in caspase-3 activation and nuclear condensation and fragmentation. PFOS exposure selectively increased activation of ERK that remained above control over 6 h. The inhibitor of ERK pathway, PD98059, substantially blocked caspase-3 activation induced by PFOS, whereas inhibitors of JNK and p38 MAPK, SP600125 and SB203580, respectively, had no effect. PKC inhibitors, bisindolylmaleimide I and Gö6976, dampened caspase-3 activity and ERK activation induced by PFOS. Collectively, it is suggested that PKC and ERK play proapoptotic roles in PFOS-induced apoptosis of cerebellar granule cells and PKC act as an upstream regulator of ERK activation.
authors.affiliation: Department of Pharmacology and Toxicology, School of Medicine, Catholic University of Daegu, Daegu, Republic of Korea.
authors.forename: Youn Ju
authors.initials: YJ
authors.lastname: Lee
authors.forename: Hyun-Gyo
authors.initials: HG
authors.lastname: Lee
authors.forename: Jae-Ho
authors.initials: JH
authors.lastname: Yang
mesh_terms: D017738:Alkanesulfonic Acids / Q000633:toxicity*; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D053148:Caspase 3 / Q000378:metabolism; D002531:Cerebellum / Q000187:drug effects*; D004785:Environmental Pollutants / Q000633:toxicity*; D005466:Fluorocarbons / Q000633:toxicity*; D020935:MAP Kinase Signaling System / Q000502:physiology*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D017738:Alkanesulfonic Acids; D004785:Environmental Pollutants; D005466:Fluorocarbons; C076994:perfluorooctane sulfonic acid; D020928:Mitogen-Activated Protein Kinases; D053148:Caspase 3