Amyloid beta peptide (25-35) activates protein kinase C leading to cyclooxygenase-2 induction and prostaglandin E2 release in primary midbrain astrocytes

Michael Hüll, Barbara Müksch, Ravi Shankar Akundi, Anne Waschbisch, Jeroen J M Hoozemans, Robert Veerhuis, Bernd L Fiebich

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Prostaglandins (PGs) are generated by the enzymatic activity of cyclooxygenase-1 and -2 (COX-1/2) and modulate several functions in the CNS such as the generation of fever, the sleep/wake cycle, and the perception of pain. Moreover, the induction of COX-2 and the generation of PGs has been linked to neuroinflammatory aspects of Alzheimer's disease (AD). Non-steroidal anti-inflammatory drugs (NSAIDs) that block COX enzymatic activity have been shown to reduce the incidence of AD in various epidemiological studies. While several reports investigated the expression of COX-2 in neurons and microglia, expression of COX-2 in astroglial cells has not been investigated in detail. Here we show that amyloid beta peptide 25-35 (Abeta(25-35)) induces COX-2 mRNA and protein synthesis and a subsequent release of prostaglandin E(2) (PGE(2)) in primary midbrain astrocytes. We further demonstrate that protein kinase C (PKC) is involved in Abeta(25-35)-induced COX-2/PGE(2) synthesis. PKC-inhibitors prevent Abeta(25-35)-induced COX-2 and PGE(2) synthesis. Furthermore Abeta(25-35) rapidly induces the phosphorylation and enzymatic activation of PKC in primary rat midbrain glial cells and in primary human astrocytes from post mortem tissue. Our data suggest that the PKC isoforms alpha and/or beta are most probably involved in Abeta(25-35)-induced expression of COX-2 in midbrain astrocytes. The potential role of astroglial cells in the phagocytosis of amyloid and the involvement of PGs in this process suggests that a modulation of PGs synthesis may be a putative target in the prevention of amyloid deposition.

Original languageEnglish
Pages (from-to)663-72
Number of pages10
JournalNeurochemistry International
Volume48
Issue number8
DOIs
Publication statusPublished - Jun 2006

Cite this

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title = "Amyloid beta peptide (25-35) activates protein kinase C leading to cyclooxygenase-2 induction and prostaglandin E2 release in primary midbrain astrocytes",
abstract = "Prostaglandins (PGs) are generated by the enzymatic activity of cyclooxygenase-1 and -2 (COX-1/2) and modulate several functions in the CNS such as the generation of fever, the sleep/wake cycle, and the perception of pain. Moreover, the induction of COX-2 and the generation of PGs has been linked to neuroinflammatory aspects of Alzheimer's disease (AD). Non-steroidal anti-inflammatory drugs (NSAIDs) that block COX enzymatic activity have been shown to reduce the incidence of AD in various epidemiological studies. While several reports investigated the expression of COX-2 in neurons and microglia, expression of COX-2 in astroglial cells has not been investigated in detail. Here we show that amyloid beta peptide 25-35 (Abeta(25-35)) induces COX-2 mRNA and protein synthesis and a subsequent release of prostaglandin E(2) (PGE(2)) in primary midbrain astrocytes. We further demonstrate that protein kinase C (PKC) is involved in Abeta(25-35)-induced COX-2/PGE(2) synthesis. PKC-inhibitors prevent Abeta(25-35)-induced COX-2 and PGE(2) synthesis. Furthermore Abeta(25-35) rapidly induces the phosphorylation and enzymatic activation of PKC in primary rat midbrain glial cells and in primary human astrocytes from post mortem tissue. Our data suggest that the PKC isoforms alpha and/or beta are most probably involved in Abeta(25-35)-induced expression of COX-2 in midbrain astrocytes. The potential role of astroglial cells in the phagocytosis of amyloid and the involvement of PGs in this process suggests that a modulation of PGs synthesis may be a putative target in the prevention of amyloid deposition.",
keywords = "Alzheimer Disease, Amyloid beta-Peptides, Animals, Animals, Newborn, Astrocytes, Cyclooxygenase 2, Dinoprostone, Encephalitis, Enzyme Activation, Enzyme Inhibitors, Humans, Mesencephalon, Peptide Fragments, Phosphorylation, Plaque, Amyloid, Protein Kinase C, Protein Kinase C beta, Protein Kinase C-alpha, RNA, Messenger, Rats, Rats, Sprague-Dawley, Journal Article, Research Support, Non-U.S. Gov't",
author = "Michael H{\"u}ll and Barbara M{\"u}ksch and Akundi, {Ravi Shankar} and Anne Waschbisch and Hoozemans, {Jeroen J M} and Robert Veerhuis and Fiebich, {Bernd L}",
year = "2006",
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volume = "48",
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journal = "Neurochemistry International",
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Amyloid beta peptide (25-35) activates protein kinase C leading to cyclooxygenase-2 induction and prostaglandin E2 release in primary midbrain astrocytes. / Hüll, Michael; Müksch, Barbara; Akundi, Ravi Shankar; Waschbisch, Anne; Hoozemans, Jeroen J M; Veerhuis, Robert; Fiebich, Bernd L.

In: Neurochemistry International, Vol. 48, No. 8, 06.2006, p. 663-72.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Amyloid beta peptide (25-35) activates protein kinase C leading to cyclooxygenase-2 induction and prostaglandin E2 release in primary midbrain astrocytes

AU - Hüll, Michael

AU - Müksch, Barbara

AU - Akundi, Ravi Shankar

AU - Waschbisch, Anne

AU - Hoozemans, Jeroen J M

AU - Veerhuis, Robert

AU - Fiebich, Bernd L

PY - 2006/6

Y1 - 2006/6

N2 - Prostaglandins (PGs) are generated by the enzymatic activity of cyclooxygenase-1 and -2 (COX-1/2) and modulate several functions in the CNS such as the generation of fever, the sleep/wake cycle, and the perception of pain. Moreover, the induction of COX-2 and the generation of PGs has been linked to neuroinflammatory aspects of Alzheimer's disease (AD). Non-steroidal anti-inflammatory drugs (NSAIDs) that block COX enzymatic activity have been shown to reduce the incidence of AD in various epidemiological studies. While several reports investigated the expression of COX-2 in neurons and microglia, expression of COX-2 in astroglial cells has not been investigated in detail. Here we show that amyloid beta peptide 25-35 (Abeta(25-35)) induces COX-2 mRNA and protein synthesis and a subsequent release of prostaglandin E(2) (PGE(2)) in primary midbrain astrocytes. We further demonstrate that protein kinase C (PKC) is involved in Abeta(25-35)-induced COX-2/PGE(2) synthesis. PKC-inhibitors prevent Abeta(25-35)-induced COX-2 and PGE(2) synthesis. Furthermore Abeta(25-35) rapidly induces the phosphorylation and enzymatic activation of PKC in primary rat midbrain glial cells and in primary human astrocytes from post mortem tissue. Our data suggest that the PKC isoforms alpha and/or beta are most probably involved in Abeta(25-35)-induced expression of COX-2 in midbrain astrocytes. The potential role of astroglial cells in the phagocytosis of amyloid and the involvement of PGs in this process suggests that a modulation of PGs synthesis may be a putative target in the prevention of amyloid deposition.

AB - Prostaglandins (PGs) are generated by the enzymatic activity of cyclooxygenase-1 and -2 (COX-1/2) and modulate several functions in the CNS such as the generation of fever, the sleep/wake cycle, and the perception of pain. Moreover, the induction of COX-2 and the generation of PGs has been linked to neuroinflammatory aspects of Alzheimer's disease (AD). Non-steroidal anti-inflammatory drugs (NSAIDs) that block COX enzymatic activity have been shown to reduce the incidence of AD in various epidemiological studies. While several reports investigated the expression of COX-2 in neurons and microglia, expression of COX-2 in astroglial cells has not been investigated in detail. Here we show that amyloid beta peptide 25-35 (Abeta(25-35)) induces COX-2 mRNA and protein synthesis and a subsequent release of prostaglandin E(2) (PGE(2)) in primary midbrain astrocytes. We further demonstrate that protein kinase C (PKC) is involved in Abeta(25-35)-induced COX-2/PGE(2) synthesis. PKC-inhibitors prevent Abeta(25-35)-induced COX-2 and PGE(2) synthesis. Furthermore Abeta(25-35) rapidly induces the phosphorylation and enzymatic activation of PKC in primary rat midbrain glial cells and in primary human astrocytes from post mortem tissue. Our data suggest that the PKC isoforms alpha and/or beta are most probably involved in Abeta(25-35)-induced expression of COX-2 in midbrain astrocytes. The potential role of astroglial cells in the phagocytosis of amyloid and the involvement of PGs in this process suggests that a modulation of PGs synthesis may be a putative target in the prevention of amyloid deposition.

KW - Alzheimer Disease

KW - Amyloid beta-Peptides

KW - Animals

KW - Animals, Newborn

KW - Astrocytes

KW - Cyclooxygenase 2

KW - Dinoprostone

KW - Encephalitis

KW - Enzyme Activation

KW - Enzyme Inhibitors

KW - Humans

KW - Mesencephalon

KW - Peptide Fragments

KW - Phosphorylation

KW - Plaque, Amyloid

KW - Protein Kinase C

KW - Protein Kinase C beta

KW - Protein Kinase C-alpha

KW - RNA, Messenger

KW - Rats

KW - Rats, Sprague-Dawley

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1016/j.neuint.2005.08.013

DO - 10.1016/j.neuint.2005.08.013

M3 - Article

VL - 48

SP - 663

EP - 672

JO - Neurochemistry International

JF - Neurochemistry International

SN - 0197-0186

IS - 8

ER -