Perfluorooctane sulfonate-induced apoptosis of cerebellar granule cells is mediated by ERK 1/2 pathway

• Published in: Chemosphere (Oxford) Vol. 90; no. 5; pp. 1597 - 1602
• Main Authors: Lee, Youn Ju, Lee, Hyun-Gyo, Yang, Jae-Ho
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 01.02.2013; Elsevier
• Subjects: Alkanesulfonic Acids - toxicity; Animals; Apoptosis; Apoptosis - physiology; Biological and medical sciences; Caspase 3 - metabolism; caspase-3; Cerebellar granule cell; Cerebellum - drug effects; Chemical and industrial products toxicology. Toxic occupational diseases; condensation; Environmental Pollutants - toxicity; enzyme activity; Fluorocarbons - toxicity; MAP Kinase Signaling System - physiology; Medical sciences; Mitogen-activated protein kinase; Mitogen-Activated Protein Kinases - metabolism; neurons; neurotoxicity; neurotoxins; Perfluorooctane sulfonate; Protein kinase C; Rats; Rats, Sprague-Dawley; Toxicology; Various organic compounds; Mitogen-activated protein kinase; Protein kinase C; Perfluorooctane sulfonate; Cerebellar granule cell; Apoptosis; Cerebellum; Rat; Toxicity; Nervous system; Persistent organic pollutant; Signal transduction; Neurotoxicity; Mechanism of action; Granule neuron; Enzyme; Organic perhalocompound; Transferases; Rodentia; In vitro; Anionic surfactant; Vertebrata; Mammalia; Cell death; Animal; Emerging pollutant; Fluorine Organic compounds
• ISSN: 0045-6535; 1879-1298
• DOI: 10.1016/j.chemosphere.2012.08.033

► Signaling pathway in PFOS-induced apoptosis was investigated. ► PFOS selectively increased ERK in cerebellar granule cells. ► PFOS-induced apoptosis was reduced by inhibition of ERK. ► PKC was an upstream regulator of ERK activation, which led to PFOS-induced apoptosis. 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 7d. 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 6h. 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.