INT256696
From wiki-pain
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Sentences Mentioned In
Key: | Protein | Mutation | Event | Anatomy | Negation | Speculation | Pain term | Disease term |
Other unknown transcription factors induced by XBP-1 or interacted with XBP-1 may have a function in the activation of WFS1 promoter. | |||||||||||||||
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Collectively, these results indicate that valproate can strongly activate the WFS1 promoter together with XBP-1 specifically in neuronal cells.
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The upregulation of WFS1 by valproate is probably regulated by the same element because the promoter lacking this sequence, pGL3-WFS1-short, did not respond to valproate (Figure 2). | |||||||||||||||
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phosphorylation levels (Figure 1A upper panel), raising the possibility that WFS1 upregulation by valproate is not regulated by the ER stress signaling network. | |||||||||||||||
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We were therefore interested in determining whether this WFS1 promoter can be activated by valproate treatment. | |||||||||||||||
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Figure 1B shows that expression levels of these ER stress markers did not change by valproate, indicating that valproate specifically upregulates WFS1 without activating other components of ER stress signaling. | |||||||||||||||
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It has been postulated that XBP-1 is important in activating the WFS1 promoter in SH-SY5Y cells [22]. | |||||||||||||||
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Another mood stabilizer, lithium, did not increase WFS1 expression levels significantly in these cells (Figure 1A, lower panel). | |||||||||||||||
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To determine whether PERK signaling is involved in WFS1 upregulation by valproate, we measured expression levels of phosphorylated eIF2? | |||||||||||||||
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Valproate increased WFS1 expression levels in a dose-dependent manner (Figure 3A, lanes 5 and 6, lower panels, input). | |||||||||||||||
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Downregulation of GRP94 may increase the amount of GRP94-free WFS1, leading to the enhancement of WFS1 function. | |||||||||||||||
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Valproate increased WFS1 protein expression levels in Neuro-2a cells with a peak at 24 hr (Figure 1A, upper panel). | |||||||||||||||
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Valproate activates the WFS1 promoter and induces WFS1 mRNA expression in neuronal cells. | |||||||||||||||
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Thus, the downregulation of GRP94 may have the same effect as the upregulation of WFS1. | |||||||||||||||
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The modulation of ER stress through the activation of WFS1 may be part of valproate's action in bipolar disorder. | |||||||||||||||
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Valproate decreased the ratio between immunoprecipiated WFS1 and GRP94 in a dose-dependent manner (Figure 3B), suggesting that WFS1 dissociates from GRP94 and that GRP94-free WFS1 is increased with valproate.
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Therapeutic concentrations of valproate induce expression of WFS1 mRNA and activate the WFS1 promoter. | |||||||||||||||
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Valproate strongly activates the promoter region of WFS1 gene. | |||||||||||||||
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It is also possible that upregulation of WFS1 by valproate increases the ratio between GRP94-free WFS1 and GRP94-bound WFS1, leading to the activation of WFS1 (Figure 4). | |||||||||||||||
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We have previously shown that the minimum element for WFS1 promoter activation under ER stress conditions. | |||||||||||||||
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General Comments
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