Figure 5 | Cell Death & Disease

Figure 5

From: Fluvoxamine alleviates ER stress via induction of Sigma-1 receptor

Figure 5

Flv suppresses ER stress-mediated apoptosis. (a) Tm, Tm+Flv, Tm+Paroxetine (Px), or Tm+Flv+NE-100 were added to Neuro2a cells. The free LDH activity was measured over the time course shown in the figure, and cytotoxicities were compared. At the times shown in the figure, cells were treated with 10 μg/ml of Flv, 1 μg/ml of Tm, 1 μg/ml of Px, and 1 μg/ml of NE-100. The cytotoxicity induced by Tm+Flv treatment was significantly lower than that induced by treatment with Tm alone. No change in cytotoxicity was observed with Tm+Px treatment. With Tm+Flv+NE-100 treatment, the effect of Flv was negated. Values are the mean±S.D. (*P<0.05, Student’s t-test; n=3). (b) Flv administration reduces the area and volume of the cerebral infarct in mice subjected to middle cerebral artery occlusion (MCAO). MCAO was performed in mice administered an intraperitoneal injection of vehicle (20 mg/kg, n=9) or Flv (20 mg/kg, n=9). Cerebral cortex slices were prepared 24 h later. (The forebrain was divided into five coronal 2-mm sections). The slices were stained with TTC, and the areas and volumes of the respective cerebral infarct lesions were compared. The photograph in the figure shows slices 4, 6, and 8 mm from the front of the brain. A significant reduction in the area of the cerebral infarct lesion was observed in Flv-treated mice. Three upper images: representative images of cortex slices from vehicle-treated mice. Three lower images: representative images of cortex slices from Flv-treated mice. (c) MCAO was performed in mice treated with Flv or vehicle. Brain slices from mice in each group were stained with TTC. The area of the cerebral infarct lesion was measured with image analysis software from a photograph of the cut surface taken with a digital camera. Using reported methods, the volume of the cerebral infarct lesion was calculated from the area of the cerebral infarct lesion measured in (b).15, 16 The volume of the cerebral infarct lesion in mice treated with Flv was significantly reduced. Values are the mean±S.D. (*P<0.05, Student’s t-test; n=3). (d) Tm (1 μg/ml) or Tm (1 μg/ml) and Flv (10 μg/ml) were added to Neuro2a cells, and CHOP expression was monitored over the time course as shown in the figure. A significant reduction in CHOP expression was observed at 2 h and 6 h with Tm+Flv treatment when compared with expression after treatment with Tm alone. CHOP expression was measured with densitometry. The results are shown in the bar graph. The 0 h time point was normalized to 1. Values are the mean±S.D. (*P<0.05, Student’s t-test; n=3). (e) Tm (1 μg/ml) or Tm (1 μg/ml) and Flv (10 μg/ml) were added to HEK293 cells, and α-caspase-4 processing was monitored over the time course shown in the figure. Processed α-caspase-4/total α-caspase-4 was measured with densitometry. The results are shown in the bar graph. With the Tm+Flv treatment, α-caspase-4 processing at 2, 6, and 24 h was significantly reduced compared with processing after treatment with Tm alone, indicating that Flv treatment reduced α-caspase-4 activation. Values are the mean±S.D. (*P<0.05, Student’s t-test; n=3)

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