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Phlorofucofuroeckol Improves Glutamate-Induced Neurotoxicity through Modulation of Oxidative Stress-Mediated Mitochondrial Dysfunction in PC12 Cells

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ABSTRACT

Stroke is a complex neurodegenerative disorder with a clinically high prevalence and mortality. Despite many efforts to protect against ischemic stroke, its incidence and related permanent disabilities continue to increase. In this study, we found that pretreatment with phlorofucofuroeckol (PFF), isolated from brown algae species, significantly increased cell viability in glutamate-stimulated PC12 cells. Additionally, glutamate-stimulated cells showed irregular morphology, but PFF pretreatment resulted in improved cell morphology, which resembled that in cells cultured under normal conditions. We further showed that PFF pretreatment effectively inhibited glutamate-induced apoptotic cell death in a caspase-dependent manner. Reactive oxygen species (ROS) induced by oxidative stress are closely associated with ischemia-induced neurological diseases. Exposure of PC12 cells to glutamate induced abundant production of intracellular ROS and mitochondrial dysfunction, which was attenuated by PFF in a dose-dependent manner. In vivo studies revealed that PFF-mediated prevention was achieved predominantly through inhibition of apoptosis and mitochondrial ROS generation. Taken together, these results suggest the possibility of PFF as a neuroprotective agent in ischemic stroke.

No MeSH data available.


Cytotoxic effect of PFF in PC12 cells.(A) Chemical structure of PFF. (B) PC12 cells were treated with increasing concentrations of PFF or a vehicle control for 24 h. Cell viability was assessed with the MTT assay. Data represent the means and SD of three independent experiments. SC, vehicle control (0.01% DMSO).
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pone.0163433.g001: Cytotoxic effect of PFF in PC12 cells.(A) Chemical structure of PFF. (B) PC12 cells were treated with increasing concentrations of PFF or a vehicle control for 24 h. Cell viability was assessed with the MTT assay. Data represent the means and SD of three independent experiments. SC, vehicle control (0.01% DMSO).

Mentions: We first isolated PFF from Ecklonia cava Kjellman (Fig 1A). Although the properties of PFF have been studied in neuronal cells [24, 25], the cytotoxic effect of Ecklonia cava Kjellman-derived PFF on PC12 cells has not been examined. We, thus, used the CCK8 assay to evaluate the dose-dependent cytotoxic effects of PFF on PC12 cells. We showed that stimulation with PFF had no significant effect on cell viability at various concentrations (1–10 μM) over 24 h (Fig 1B). Thus, we used PFF at a concentration of 10 μM in the following experiments.


Phlorofucofuroeckol Improves Glutamate-Induced Neurotoxicity through Modulation of Oxidative Stress-Mediated Mitochondrial Dysfunction in PC12 Cells
Cytotoxic effect of PFF in PC12 cells.(A) Chemical structure of PFF. (B) PC12 cells were treated with increasing concentrations of PFF or a vehicle control for 24 h. Cell viability was assessed with the MTT assay. Data represent the means and SD of three independent experiments. SC, vehicle control (0.01% DMSO).
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC5036853&req=5

pone.0163433.g001: Cytotoxic effect of PFF in PC12 cells.(A) Chemical structure of PFF. (B) PC12 cells were treated with increasing concentrations of PFF or a vehicle control for 24 h. Cell viability was assessed with the MTT assay. Data represent the means and SD of three independent experiments. SC, vehicle control (0.01% DMSO).
Mentions: We first isolated PFF from Ecklonia cava Kjellman (Fig 1A). Although the properties of PFF have been studied in neuronal cells [24, 25], the cytotoxic effect of Ecklonia cava Kjellman-derived PFF on PC12 cells has not been examined. We, thus, used the CCK8 assay to evaluate the dose-dependent cytotoxic effects of PFF on PC12 cells. We showed that stimulation with PFF had no significant effect on cell viability at various concentrations (1–10 μM) over 24 h (Fig 1B). Thus, we used PFF at a concentration of 10 μM in the following experiments.

View Article: PubMed Central - PubMed

ABSTRACT

Stroke is a complex neurodegenerative disorder with a clinically high prevalence and mortality. Despite many efforts to protect against ischemic stroke, its incidence and related permanent disabilities continue to increase. In this study, we found that pretreatment with phlorofucofuroeckol (PFF), isolated from brown algae species, significantly increased cell viability in glutamate-stimulated PC12 cells. Additionally, glutamate-stimulated cells showed irregular morphology, but PFF pretreatment resulted in improved cell morphology, which resembled that in cells cultured under normal conditions. We further showed that PFF pretreatment effectively inhibited glutamate-induced apoptotic cell death in a caspase-dependent manner. Reactive oxygen species (ROS) induced by oxidative stress are closely associated with ischemia-induced neurological diseases. Exposure of PC12 cells to glutamate induced abundant production of intracellular ROS and mitochondrial dysfunction, which was attenuated by PFF in a dose-dependent manner. In vivo studies revealed that PFF-mediated prevention was achieved predominantly through inhibition of apoptosis and mitochondrial ROS generation. Taken together, these results suggest the possibility of PFF as a neuroprotective agent in ischemic stroke.

No MeSH data available.