Effects of perfluorooctane sulfonate on ion channels and glutamate-activated current in cultured rat hippocampal neurons

Liao, Chunyang; Cui, Lin; Zhou, Qunfang; Duan, Shumin; Jiang, Guibin

doi:10.1016/j.etap.2008.11.013

Cited by 36 publications

(20 citation statements)

References 45 publications

(55 reference statements)

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“…Although exposure duration in our study was shorter and no cytotoxicity was observed, the increase in spike and burst activity following acute exposure of rat primary cortical neurons to a high PFOS concentration could be indicative of the onset of excitotoxicity. Another potential explanation for the inhibition of activity in the hiPSC-derived neuronal cultures could reside in the PFOS-induced shift in the activation curves of voltage-gated sodium channels towards hyperpolarization 37,69 , making it harder for the cell to reach an action potential. Future research to elucidate the possible counteracting mechanisms of action observed in our network study of PFOS and PFOA could focus on patch-clamp studies in neuronal networks following both acute and chronic exposure.…”

Section: Discussionmentioning

confidence: 99%

“…At (high) micromolar concentrations, PFOS and/or PFOA can affect a range of (pre)-synaptic processes, including reduction of cell viability [26][27][28][29] , altered neuronal differentiation 30 , increased formation of reactive oxygen species 27,28,[31][32][33][34] , and increased intracellular calcium (Ca 2+ ) concentrations 35,36 . In addition, PFOS and PFOA may also affect postsynaptic processes, including altered glutamate-activated currents and increase of potassium currents 37,38 . By inducing influx of Ca 2+ through voltage-dependent calcium channels, PFOS may exhibit acute excitotoxic effects on synaptic function and chronically inhibit synaptogenesis in rat brain hippocampal neurons 39 .…”

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confidence: 99%

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Perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) acutely affect human α1β2γ2L GABAA receptor and spontaneous neuronal network function in vitro

Tukker

Bouwman

Kleef

et al. 2020

Sci Rep

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Concerns about the neurotoxic potential of polyfluoroalkyl substances (PFAS) such as perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) increase, although their neurotoxic mechanisms of action remain debated. Considering the importance of the GABA A receptor in neuronal function, we investigated acute effects of PFAS on this receptor and on spontaneous neuronal network activity. PFOS (Lowest Observed Effect Concentration (LOEC) 0.1 µM) and PFOA (LOEC 1 µM) inhibited the GABA-evoked current and acted as non-competitive human GABA A receptor antagonists. Network activity of rat primary cortical cultures increased following exposure to PFOS (LOEC 100 µM). However, exposure of networks of human induced pluripotent stem cell (hiPSC)-derived neurons decreased neuronal activity. The higher sensitivity of the α 1 β 2 γ 2L GABA A receptor for PFAS as compared to neuronal networks suggests that PFAS have additional mechanisms of action, or that compensatory mechanisms are at play. Differences between rodent and hiPSC-derived neuronal networks highlight the importance of proper model composition. LOECs for PFAS on GABA A receptor and neuronal activity reported here are within or below the range found in blood levels of occupationally exposed humans. For PFOS, LOECs are even within the range found in human serum and plasma of the general population, suggesting a clear neurotoxic risk. Perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) are well-known perfluoroalkyl substances (PFAS) consisting of an eight-carbon chain in which hydrogen atoms have been substituted with fluorine. Their combined hydrophobic, hydrophilic, oleophobic and lipophobic properties make them ideal industrial surfactants for the manufacturing of consumer products, including paint, stain repellents, fire-fighting foams, and non-stick cookware coatings. The strong carbon-fluorine bond renders PFOS and PFOA highly persistent and studies have shown their presence in the environment, wildlife and even human blood (for reviews see 1,2). By 2002, production of PFOS was phased out and production phase out of PFOA followed in 2006 3. Recent studies indicate that these efforts may be responsible for a reduction in human blood levels in some areas, but the long half-lives of PFOS and PFOA result in slow elimination from environment and humans 4,5. Research has demonstrated that the (developing) nervous system is one of the most sensitive targets for PFOS and PFOA. In mice and rats exposed pre-and/or neonatally to PFOS or PFOA, increased motor activity, decreased habituation and deficits in spatial learning and memory abilities have been observed 6-11. Developmental neurotoxicity has also been observed in other species, including chicken 12 and zebrafish larvae 13,14. However, epidemiological studies have been inconclusive on the risks of PFAS exposure on neurodevelopment. Some studies indicate an association between prenatal PFOS and/or PFOA exposure and an increased risk on congenital cerebral palsy 15 , neuro-behavioural developmen...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) acutely affect human α1β2γ2L GABAA receptor and spontaneous neuronal network function in vitro

Tukker

Bouwman

Kleef

et al. 2020

Sci Rep

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“…The toxicological effects of PFOS have been reported numerous times, mainly based on in vivo and in vitro mammalian studies. The liver, lung and kidney might serve as the main target organs (Seacat et al, 2002;Liao et al, 2009). Some research has investigated whether prenatal exposure of PFOS causes neonatal rat lung morphological changes and rat early death, which may be involved in inhibiting lung maturation (Grasty et al, 2003(Grasty et al, , 2005.…”

Section: Introductionmentioning

confidence: 99%

Perfluorooctane sulfonate induces apoptosis in lung cancer A549 cells through reactive oxygen species‐mediated mitochondrion‐dependent pathway

Mao

Xia

Wang

et al. 2012

J of Applied Toxicology

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Perfluorooctane sulfonate (PFOS) is a widespread environmental contaminant that is detected in the lung of mammals. The mechanisms underlying PFOS-induced lung cytotoxicity remain unclear. The main purpose of this study was to evaluate the cytotoxic effects of PFOS on human lung cancer A549 cells and its possible molecular mechanism. A549 cells were treated with PFOS (0, 25, 50, 100 and 200 μm) and the cellular apoptosis, mitochondrial membrane potential as well as intracellular reactive oxygen species were determined. In this study, PFOS induced a dose-dependent increase in A549 cell toxicity via an apoptosis pathway as characterized by increased percentage of sub-G1, activation of caspase-3 and -9, and increased ratio of Bax/bcl-2 mRNA expression. In addition, there was obvious oxidative stress, represented by decreased glutathione level, increased malondialdehyde level and superoxide dismutase activity. N-Acetylcysteine, as an antioxidant that is a direct reactive oxygen species scavenger, can effectively block PFOS-induced reactive oxygen species generation, mitochondrial membrane potential loss and cell apoptosis. These data indicate that PFOS induces apoptosis in A549 cells through a reactive oxygen species-mediated mitochondrial dysfunction pathway mechanism.

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“…The cells were cultured in a cell bottle for several days, during which cell culture medium was changed every other day, and the cells were subcultured until the cells were fully differentiated. The differentiated PC12 cells were treated with 0.05%DMSO or different concentrations of PFOS (10, 50, 100, 150 and 200 μM) for 48 hr, or with 100 μM PFOS for 0, 12, 24, 36, 48 hr (Liao et al, 2009;Liao et al, 2008). PFOS was dissolved in DMSO.…”

Section: Cell Culture and Treatmentmentioning

confidence: 99%

Perﬂuorooctane sulfonate induces apoptosis via activation of FoxO3a and upregulation of proapoptotic Bcl-2 proteins in PC12 cells

Ding²,

Yan

et al. 2019

J. Toxicol. Sci.

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Perfluorooctane sulfonate (PFOS), a kind of organic pollutant widely found in the environment and biota, could alter normal brain development and produce cognitive dysfunction. For the past years, the neurotoxic effects of PFOS have been shown. Recent studies have proven that PFOS can induce neuronal apoptosis and cause neurotoxicity, but the regulatory proteins referred to the process have not been clarified. In this study, PC12 cells were used to investigate the changes of the expression of apoptosis-related proteins, forkhead box O3 (FoxO3a) and pro-apoptotic Bcl-2 proteins. We detected that the levels of cleaved caspase-3 and cleaved PARP were up-regulated obviously in PFOS-treated PC12 cells by using Western blotting, and that the apoptotic rate of PC12 cells was increased significantly by using flow cytometry, verifying that PFOS could induce neuronal apoptosis. Western blot analysis and immunofluorescence revealed obvious up-regulation of the expression of FoxO3a and proapoptotic Bcl-2 proteins. In addition, knockdown of FoxO3a gene inhibited Bim expression and apoptosis. According to the data, we believe that FoxO3a may play a crucial role in PFOS-induced neurotoxicity.

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Effects of perfluorooctane sulfonate on ion channels and glutamate-activated current in cultured rat hippocampal neurons

Cited by 36 publications

References 45 publications

Perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) acutely affect human α1β2γ2L GABAA receptor and spontaneous neuronal network function in vitro

Perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) acutely affect human α1β2γ2L GABAA receptor and spontaneous neuronal network function in vitro

Perfluorooctane sulfonate induces apoptosis in lung cancer A549 cells through reactive oxygen species‐mediated mitochondrion‐dependent pathway

Perﬂuorooctane sulfonate induces apoptosis via activation of FoxO3a and upregulation of proapoptotic Bcl-2 proteins in PC12 cells

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