Perfluorooctane Sulfonate Induces Apoptosis in N9 Microglial Cell Line

Zhang, Ling; Li, Yuanyuan; Zeng, Huai-cai; Li, Miao; Wan, Yanjian; Schluesener, Hermann J.; Zhang, Zhiyuan; Xu, Shunqing

doi:10.1177/1091581810387832

Cited by 25 publications

(18 citation statements)

References 42 publications

(46 reference statements)

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“…In SH-SY5Y cells, our results show that PFOS induced cell damage and caused a decrease in cell viability. It is in line with previous studies in N9 cells and HepG2 cells [47] , [48] . In addition, PFOS-induced apoptosis was raised in a dose-dependent manner.…”

Section: Discussionsupporting

confidence: 93%

Chronic Exposure to Perfluorooctane Sulfonate Induces Behavior Defects and Neurotoxicity through Oxidative Damages, In Vivo and In Vitro

Chen

et al. 2014

PLoS ONE

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Perfluorooctane sulfonate (PFOS) is an emerging persistent pollutant which shows multiple adverse health effects. However, the neurotoxicity of PFOS and its mechanisms have not been fully elucidated. Using a combination of in vivo and in vitro methods, the present study provides a detailed description of PFOS-induced neurotoxicity. Results showed that the median lethal concentration of PFOS was 2.03 mM in Caenorhabditis elegans for 48 h exposure. 20 µM PFOS caused decrease of locomotor behaviors including forward movement, body bend and head thrash. Additionally, PFOS exposure reduced chemotaxis index of C. elegans, which indicates the decline of chemotaxis learning ability. Using green fluorescent protein (GFP) labelled transgenic strains, we found that PFOS caused down-regulated expression of a chemoreceptor gene, gcy-5, in ASE chemosensory neurons, but did not affect cholinergic neurons and dopaminergic neurons. In SH-SY5Y cells, 48 h exposure to 25 µM and 50 µM PFOS induced cell damage, apoptosis and the reactive oxygen species (ROS) generation. PFOS caused significant increases of lipid peroxidation and superoxide dismutase activity, but an actual decrease of glutathione peroxidase activity. Furthermore, antioxidant N-acetylcysteine rescued cells from PFOS-induced apoptosis via blocking ROS. Our results demonstrate that chronic exposure to PFOS can cause obvious neurotoxicity and behavior defects. Oxidative damage and anti-oxidative deficit are crucial mechanisms in neurotoxicity of PFOS.

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Section: Discussionsupporting

confidence: 93%

Chronic Exposure to Perfluorooctane Sulfonate Induces Behavior Defects and Neurotoxicity through Oxidative Damages, In Vivo and In Vitro

Chen

et al. 2014

PLoS ONE

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“…The result obtained from the MTT assay indicates that PFOS induces a concentration‐ and time‐dependent cytotoxicity in A549 cells. This observation is consistent with previous reports that PFOS causes cytotoxicity against N9 cells and HepG2 cells (Hu and Hu, ; Zhang et al ., ). From the MTT assay in our study, the high concentration of PFOS (200 μ m ) caused 40% decrease in cell viability compared with the control group, but the levels of LDH release in all groups were not significantly different from the control.…”

Section: Discussionmentioning

confidence: 97%

“…Various intrinsic and extrinsic factors are involved in regulating this process (Fuchs and Steller, 2011). It has been reported that PFOS exposure can promote apoptosis in a murine N9 cell line, a human Hep G2 cell line and fish primary cultured hepatocytes (Liu et al, 2007;Hu and Hu, 2009;Shi and Zhou, 2010;Chen et al, 2012;Zhang et al, 2011). Mitochondria have been shown play an essential role in triggering apoptosis.…”

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 mechanism(s) underlying the observed neurotoxicity have been studied in vitro in neuronal cells. 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 .…”

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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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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Perfluorooctane Sulfonate Induces Apoptosis in N9 Microglial Cell Line

Cited by 25 publications

References 42 publications

Chronic Exposure to Perfluorooctane Sulfonate Induces Behavior Defects and Neurotoxicity through Oxidative Damages, In Vivo and In Vitro

Chronic Exposure to Perfluorooctane Sulfonate Induces Behavior Defects and Neurotoxicity through Oxidative Damages, In Vivo and In Vitro

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

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

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