Distribution of cyclooxygenase-1 and cyclooxygenase-2 mRNAs and proteins in human brain and peripheral organs

Yasojima, Koji; Schwab, Claudia; McGeer, Edith G.; McGeer, Patrick L.

doi:10.1016/s0006-8993(99)01389-x

Cited by 232 publications

(140 citation statements)

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“…Yosojima et al . (Yasojima et al ., 1999) reported that COX‐2 was substantially upregulated in the affected areas of AD brains. In addition, COX‐2 is responsible for the systemic synthesis of PGI 2 (McAdam et al ., 1999).…”

Section: Discussionmentioning

confidence: 99%

Prostaglandin I ₂ upregulates the expression of anterior pharynx‐defective‐1α and anterior pharynx‐defective‐1β in amyloid precursor protein/presenilin 1 transgenic mice

et al. 2016

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SummaryCyclooxygenase‐2 (COX‐2) has been recently identified to be involved in the pathogenesis of Alzheimer's disease (AD). Yet, the role of an important COX‐2 metabolic product, prostaglandin (PG) I2, in the pathogenesis of AD remains unknown. Using human‐ and mouse‐derived neuronal cells as well as amyloid precursor protein/presenilin 1 (APP/PS1) transgenic mice as model systems, we elucidated the mechanism of anterior pharynx‐defective (APH)‐1α and pharynx‐defective‐1β induction. In particular, we found that PGI 2 production increased during the course of AD development. Then, PGI 2 accumulation in neuronal cells activates PKA/CREB and JNK/c‐Jun signaling pathways by phosphorylation, which results in APH‐1α/1β expression. As PGI 2 is an important metabolic by‐product of COX‐2, its suppression by NS398 treatment decreases the expression of APH‐1α/1β in neuronal cells and APP/PS1 mice. More importantly, β‐amyloid protein (Aβ) oligomers in the cerebrospinal fluid (CSF) of APP/PS1 mice are critical for stimulating the expression of APH‐1α/1β, which was blocked by NS398 incubation. Finally, the induction of APH‐1α/1β was confirmed in the brains of patients with AD. Thus, these findings not only provide novel insights into the mechanism of PGI 2‐induced AD progression but also are instrumental for improving clinical therapies to combat AD.

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Section: Discussionmentioning

confidence: 99%

Prostaglandin I ₂ upregulates the expression of anterior pharynx‐defective‐1α and anterior pharynx‐defective‐1β in amyloid precursor protein/presenilin 1 transgenic mice

et al. 2016

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“…COX-2 expression may be further induced in astrocytes and microglia in response to elevated A␤42 and/or IL-1␤ during aging or in AD (5-9), because both cytokines and ROS trigger NF-Bp50/p65-mediated transcription from COX-2 and related inflammatory genes (9 -14). Moreover, although the majority of gene transcripts are down-regulated in AD hippocampus (4,9,13,21,43,44), certain RNAs encoding inflammatory mediators exhibit overexpression (7)(8)(9)(10)(11)(12)(13). COX-2 and PS1 RNA message in human embryonic (E7-E30) and adult (1-75 years) brain coincides with the most active neurogenesis, followed by coordinate downregulation of COX-2 and PS1 RNA abundance during aging (r 2 ϭ 0.9, p Ͻ 0.03; Fig.…”

Section: Cox-2 and Ps1mentioning

confidence: 95%

“…Expression of the inducible, membrane-associated prostaglandin (PG) endoperoxide synthase cyclooxygenase-2 (COX-2), which catalyzes the rate-limiting step in the generation of pro-inflammatory PGs and eicosanoids, is up-regulated in AD (7)(8)(9)(10)(11), and transgenic mice overexpressing human COX-2 in hippocampal neurons develop neuronal apoptosis and cognitive deficits in an age-dependent manner (11)(12)(13)(14). Presenilin-1 (PS1) and PS1 C-terminal fragments, integral membrane proteins that are developmentally expressed during neurogenesis, function in the generation of amyloidogenic A␤ peptides from ␤-amyloid precursor protein (␤APP) (15)(16)(17)(18).…”

mentioning

confidence: 99%

Cyclooxygenase-2 and Presenilin-1 Gene Expression Induced by Interleukin-1β and Amyloid β42 Peptide Is Potentiated by Hypoxia in Primary Human Neural Cells

Bazán

Lukiw

2002

Journal of Biological Chemistry

117

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Inflammatory signaling networks are activated at the onset of neurodegeneration in Alzheimer's disease (AD) 1 brain (1-6).Expression of the inducible, membrane-associated prostaglandin (PG) endoperoxide synthase cyclooxygenase-2 (COX-2), which catalyzes the rate-limiting step in the generation of pro-inflammatory PGs and eicosanoids, is up-regulated in AD (7-11), and transgenic mice overexpressing human COX-2 in hippocampal neurons develop neuronal apoptosis and cognitive deficits in an age-dependent manner (11-14). Presenilin-1 (PS1) and PS1 C-terminal fragments, integral membrane proteins that are developmentally expressed during neurogenesis, function in the generation of amyloidogenic A␤ peptides from ␤-amyloid precursor protein (␤APP) (15-18). Transgenic animals bearing PS1 mutations or PS1/␤APP doubly transgenic animals display accelerated A␤ generation and microglial activation that increase synchronously with A␤ deposition (14 -19). As a consequence, hundred-fold increases in microglialderived IL-1␤, related cytokines, and pro-inflammatory lipid mediators form an amplifying cascade of brain inflammatory response (6, 20 -23). Microglial cytokine hyperactivation strongly correlates with increased ␤APP processing and aggregation of A␤ peptides into neurotoxic senile plaques, the neuropathologic hallmark of AD brain (12,(15)(16)(17).During the microglial-mediated inflammatory response to A␤ deposition in AD, overexpression of IL-1␤ not only further promotes amyloidogenesis (20 -23) but also induces an oxygensensitive transcription factor (TF) series that includes AP1, STAT1␣, and NF-Bp50/p65 (24 -27). In the human association neocortex in AD, DNA-binding activities for these TFs, as well as IL-1␤, are sharply elevated (9,24,26). Therefore, IL-1␤-triggered AP1-, NF-Bp50/p65-, and STAT1␣-sensitive genes have strong potential to propagate inflammatory signaling in the brain (20 -27). Although IL-1␤ up-regulates both ␤APP and COX-2 gene transcription and post-translational processing of ␤APP into neurotoxic A␤ peptides (20 -23, 27), IL-1␤-triggered neural inflammation may also be induced by hypoxia (28 -30). The hypoxia-inducible factor (HIF-1, a heterodimeric DNAbinding protein consisting of a cytokine-, oxygen-and growth factor-regulated HIF-1␣ and a constitutive HIF-1␤/aryl hydrocarbon receptor nuclear transporter element) normally promotes the expression of adaptive genes under hypoxic conditions. However, during pathophysiologic conditions involving ischemia and/or hypoxia, HIF-1␣ overexpression drives aberrant gene expression with rapid progression to the lethal phenotype (28,29). It is interesting that IL-1␤ partially mimics cellular hypoxia, leading to increased HIF-1␣-DNA binding and activation of COX-2 and PS2 in human gingival and syno-

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“…Inflammatory stimuli such as lipopolysaccharide (LPS) and cytokines such as TNF␣ and IL-1␤ have been found to enhance COX-2 expressions in microglia (Minghetti and Levi, 1995;Bauer et al, 1997). In pathological conditions, elevated COX-2 expressions have been observed in AD brain and ALS spinal cord (Ho et al, 1999;Yasojima et al, 1999Yasojima et al, , 2001.…”

Section: Introductionmentioning

confidence: 99%

Differential activation of subtype purinergic receptors modulates Ca²⁺ mobilization and COX‐2 in human microglia

Choi

Hong

Ryu

et al. 2003

Glia

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KEY WORDShuman microglia; adenosine triphosphate; P 2Y and P 2X receptors; COX-2, store-operated channel Ca 2ϩ entry ABSTRACTWe have studied modulation of purinergic receptors (P 2Y and P 2X subtypes) on changes in intracellular Ca 2ϩ [Ca 2ϩ ] i and expression and production of COX-2 in human microglia. Measurements using Ca 2ϩ -sensitive spectrofluorometry showed adenosine triphosphate (ATP) to cause rapid transient increases in [Ca 2ϩ ] i . Application of ATP plus the P 2X antagonist, pyridoxal-phosphate-6-azophenyl-2Ј,4Ј-disulfonic acid (PPADS), or treatment with adenosine diphosphate-␤-S (ADP-␤-S), a selective P 2Y agonist, led to a considerable prolongation in [Ca 2ϩ ] i responses compared with ATP. The prolonged time courses were consistent with sustained activation of store-operated channels (SOC) since SKF96365, an inhibitor of SOC, blocked this component of the response. RT-PCR data showed that microglia expressed no COX-2 either constitutively or following treatment of cells with ATP (100 M for 8 h). However, treatment using ATP plus PPADS or with ADP-␤-S led to marked expression of COX-2. The enhanced COX-2 with ATP plus PPADS treatment was absent in the presence of SKF96365 or using Ca 2ϩ -free solution. Immunocytochemistry, using a specific anti-COX-2 antibody, also revealed a pattern of purinergic modulation whereby lack of P 2X activation enhanced the production of COX-2 protein. These results suggest that modulation of subtypes of purinergic receptors regulates COX-2 in human microglia with a link involving SOCmediated influx of Ca 2ϩ .

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Distribution of cyclooxygenase-1 and cyclooxygenase-2 mRNAs and proteins in human brain and peripheral organs

Cited by 232 publications

References 34 publications

Prostaglandin I ₂ upregulates the expression of anterior pharynx‐defective‐1α and anterior pharynx‐defective‐1β in amyloid precursor protein/presenilin 1 transgenic mice

Prostaglandin I ₂ upregulates the expression of anterior pharynx‐defective‐1α and anterior pharynx‐defective‐1β in amyloid precursor protein/presenilin 1 transgenic mice

Cyclooxygenase-2 and Presenilin-1 Gene Expression Induced by Interleukin-1β and Amyloid β42 Peptide Is Potentiated by Hypoxia in Primary Human Neural Cells

Differential activation of subtype purinergic receptors modulates Ca²⁺ mobilization and COX‐2 in human microglia

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Distribution of cyclooxygenase-1 and cyclooxygenase-2 mRNAs and proteins in human brain and peripheral organs

Cited by 232 publications

References 34 publications

Prostaglandin I 2 upregulates the expression of anterior pharynx‐defective‐1α and anterior pharynx‐defective‐1β in amyloid precursor protein/presenilin 1 transgenic mice

Prostaglandin I 2 upregulates the expression of anterior pharynx‐defective‐1α and anterior pharynx‐defective‐1β in amyloid precursor protein/presenilin 1 transgenic mice

Cyclooxygenase-2 and Presenilin-1 Gene Expression Induced by Interleukin-1β and Amyloid β42 Peptide Is Potentiated by Hypoxia in Primary Human Neural Cells

Differential activation of subtype purinergic receptors modulates Ca2+ mobilization and COX‐2 in human microglia

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Prostaglandin I ₂ upregulates the expression of anterior pharynx‐defective‐1α and anterior pharynx‐defective‐1β in amyloid precursor protein/presenilin 1 transgenic mice

Prostaglandin I ₂ upregulates the expression of anterior pharynx‐defective‐1α and anterior pharynx‐defective‐1β in amyloid precursor protein/presenilin 1 transgenic mice

Differential activation of subtype purinergic receptors modulates Ca²⁺ mobilization and COX‐2 in human microglia