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Palmitoylethanolamide counteracts reactive astrogliosis induced by β-amyloid peptide.

Scuderi C, Esposito G, Blasio A, Valenza M, Arietti P, Steardo L, Carnuccio R, De Filippis D, Petrosino S, Iuvone T, Di Marzo V, Steardo L - J. Cell. Mol. Med. (2011)

Bottom Line: This effect was reduced by PPAR-α antagonist.Moreover, this ALIAmide, like Aβ, increased 2-AG levels.These results indicate that PEA exhibits anti-inflammatory properties able to counteract Aβ-induced astrogliosis, and suggest novel treatment for neuroinflammatory/ neurodegenerative processes.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology and Pharmacology, Sapienza University of Rome, Rome, Italy.

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Related in: MedlinePlus

PEA inhibits the Aβ-induced activation of NF-κB and AP-1 nuclear transcription factors. Aβ-challenged (1 μg/ml) cells were treated with PEA (10−7 M) in the presence of the selective PPAR-γ antagonist (GW9662, 9 nM) or the selective PPAR-α antagonist (MK886, 3 μM). Nuclear transcription factors activation was evaluated after 30 min. of treatments by EMSA analysis. Figure shows the results of NF-κB and AP-1 complex shifts (upper panel) and densitometric analysis of corresponding bands (lower panel). Treatment of astrocytes with Aβ induced the activation of the nuclear factors NF-κB and AP-1 (lines 2). PEA significantly inhibited this effect (lines 3). This inhibition was attenuated by the PPAR-α antagonist, MK886, in a partial, although significant, manner (lines 5). Each bar shows the mean ± S.E.M. of n = 3 separate experiments. ***P < 0.001 versus control; ###P < 0.001 versus Aβ-challenged cells; °°P < 0.01 and °P < 0.05 versus Aβ+ PEA-challenged cells.
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fig05: PEA inhibits the Aβ-induced activation of NF-κB and AP-1 nuclear transcription factors. Aβ-challenged (1 μg/ml) cells were treated with PEA (10−7 M) in the presence of the selective PPAR-γ antagonist (GW9662, 9 nM) or the selective PPAR-α antagonist (MK886, 3 μM). Nuclear transcription factors activation was evaluated after 30 min. of treatments by EMSA analysis. Figure shows the results of NF-κB and AP-1 complex shifts (upper panel) and densitometric analysis of corresponding bands (lower panel). Treatment of astrocytes with Aβ induced the activation of the nuclear factors NF-κB and AP-1 (lines 2). PEA significantly inhibited this effect (lines 3). This inhibition was attenuated by the PPAR-α antagonist, MK886, in a partial, although significant, manner (lines 5). Each bar shows the mean ± S.E.M. of n = 3 separate experiments. ***P < 0.001 versus control; ###P < 0.001 versus Aβ-challenged cells; °°P < 0.01 and °P < 0.05 versus Aβ+ PEA-challenged cells.

Mentions: Further experiments were aimed at investigating whether the increase in the production of inflammatory factors induced by Aβ was dependent on the activation of the MAPK pathway. Activation of the MAPKs, p38 MAPK and JNK, was measured by quantifying the level of phosphorylation of each kinase by Western blot 30 min. after the exposure to Aβ (Fig. 4). Treatment of astrocytes with Aβ resulted in an increase in the level of phosphorylation of the kinases, and it was accompanied with the activation of the nuclear factor NF-κB and AP-1, as shown by EMSA analysis (Fig. 5). PEA significantly inhibited MAPK phosphorylation and nuclear transcription factors, NF-κB and AP-1. This inhibition was attenuated by the PPAR-α antagonist, MK886, in a partly, although significant, manner.


Palmitoylethanolamide counteracts reactive astrogliosis induced by β-amyloid peptide.

Scuderi C, Esposito G, Blasio A, Valenza M, Arietti P, Steardo L, Carnuccio R, De Filippis D, Petrosino S, Iuvone T, Di Marzo V, Steardo L - J. Cell. Mol. Med. (2011)

PEA inhibits the Aβ-induced activation of NF-κB and AP-1 nuclear transcription factors. Aβ-challenged (1 μg/ml) cells were treated with PEA (10−7 M) in the presence of the selective PPAR-γ antagonist (GW9662, 9 nM) or the selective PPAR-α antagonist (MK886, 3 μM). Nuclear transcription factors activation was evaluated after 30 min. of treatments by EMSA analysis. Figure shows the results of NF-κB and AP-1 complex shifts (upper panel) and densitometric analysis of corresponding bands (lower panel). Treatment of astrocytes with Aβ induced the activation of the nuclear factors NF-κB and AP-1 (lines 2). PEA significantly inhibited this effect (lines 3). This inhibition was attenuated by the PPAR-α antagonist, MK886, in a partial, although significant, manner (lines 5). Each bar shows the mean ± S.E.M. of n = 3 separate experiments. ***P < 0.001 versus control; ###P < 0.001 versus Aβ-challenged cells; °°P < 0.01 and °P < 0.05 versus Aβ+ PEA-challenged cells.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4373435&req=5

fig05: PEA inhibits the Aβ-induced activation of NF-κB and AP-1 nuclear transcription factors. Aβ-challenged (1 μg/ml) cells were treated with PEA (10−7 M) in the presence of the selective PPAR-γ antagonist (GW9662, 9 nM) or the selective PPAR-α antagonist (MK886, 3 μM). Nuclear transcription factors activation was evaluated after 30 min. of treatments by EMSA analysis. Figure shows the results of NF-κB and AP-1 complex shifts (upper panel) and densitometric analysis of corresponding bands (lower panel). Treatment of astrocytes with Aβ induced the activation of the nuclear factors NF-κB and AP-1 (lines 2). PEA significantly inhibited this effect (lines 3). This inhibition was attenuated by the PPAR-α antagonist, MK886, in a partial, although significant, manner (lines 5). Each bar shows the mean ± S.E.M. of n = 3 separate experiments. ***P < 0.001 versus control; ###P < 0.001 versus Aβ-challenged cells; °°P < 0.01 and °P < 0.05 versus Aβ+ PEA-challenged cells.
Mentions: Further experiments were aimed at investigating whether the increase in the production of inflammatory factors induced by Aβ was dependent on the activation of the MAPK pathway. Activation of the MAPKs, p38 MAPK and JNK, was measured by quantifying the level of phosphorylation of each kinase by Western blot 30 min. after the exposure to Aβ (Fig. 4). Treatment of astrocytes with Aβ resulted in an increase in the level of phosphorylation of the kinases, and it was accompanied with the activation of the nuclear factor NF-κB and AP-1, as shown by EMSA analysis (Fig. 5). PEA significantly inhibited MAPK phosphorylation and nuclear transcription factors, NF-κB and AP-1. This inhibition was attenuated by the PPAR-α antagonist, MK886, in a partly, although significant, manner.

Bottom Line: This effect was reduced by PPAR-α antagonist.Moreover, this ALIAmide, like Aβ, increased 2-AG levels.These results indicate that PEA exhibits anti-inflammatory properties able to counteract Aβ-induced astrogliosis, and suggest novel treatment for neuroinflammatory/ neurodegenerative processes.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology and Pharmacology, Sapienza University of Rome, Rome, Italy.

Show MeSH
Related in: MedlinePlus