Evidence for Cyclooxygenase-2 Association with Caveolin-3 in Primary Cultured Rat Chondrocytes

Kwak, Jooyoung; Lee, Woon Kyu; Kim, Hyun Woo; Jung, Seung Min; Oh, Kwang Jin; Jung, Sang Yong; Huh, Yang Hoon; Ho, Seok

doi:10.3346/jkms.2006.21.1.100

Cited by 9 publications

(5 citation statements)

References 30 publications

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“…Examples of caveolae facilitated targeting of proteins involved in pro-inflammatory signal transduction include activators of p44/p42 (ERK) MAPK pathway, H-Ras [30, 31], non-receptor tyrosine kinase c-Src [31], and the upstream regulator of NF-κB, IkappaB kinase (IKK) [32]. Furthermore, caveolins have been reported to co-localize with cyclooxygenase, suggesting that caveolins play a role in regulating the function of this enzyme [33, 34]. …”

Section: Introductionmentioning

confidence: 99%

The role of fatty acids and caveolin-1 in tumor necrosis factor α–induced endothelial cell activation

et al. 2008

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Hypertriglyceridemia and associated high circulating free fatty acids are important risk factors of atherosclerosis. In contrast to omega-3 fatty acids, linoleic acid, the major omega-6 unsaturated fatty acid in the American diet, may be atherogenic by amplifying an endothelial inflammatory response. We hypothesize that omega-6 and omega-3 fatty acids can differentially modulate TNF-α-induced endothelial cell activation and that functional plasma membrane microdomains called caveolae are required for endothelial cell activation. Caveolae are particularly abundant in endothelial cells and play a major role in endothelial trafficking and the regulation of signaling pathways associated with the pathology of vascular diseases. To test our hypothesis, endothelial cells were pre-enriched with either linoleic acid or α-linolenic acid prior to TNF-α-induced endothelial activation. Measurements included oxidative stress and NF-κB-dependent induction of COX-2 and PGE2 under experimental conditions with intact caveolae and with cells in which caveolin-1 was silenced by siRNA. Exposure to TNF-α induced oxidative stress and inflammatory mediators, such as p38 MAPK, NF-κB, COX-2 and PGE2, which were all amplified by pre-enrichment with linoleic acid but blocked or reduced by α-linolenic acid. The p38 MAPK inhibitor SB203580 blocked TNF-α-mediated induction of COX-2 protein expression, suggesting a regulatory mechanism through p38 MAPK signaling. Image overlay demonstrated TNF-α-induced co-localization of TNF receptor type 1 (TNFR-1) with caveolin-1. Caveolin-1 was significantly induced by TNF-α, which was further amplified by linoleic acid and blocked by α-linolenic acid. Furthermore, silencing of the caveolin-1 gene completely blocked TNF-α-induced production of COX-2 and PGE2 and significantly reduced the amplified response of linoleic acid plus TNF-α. These data suggest that omega-6 and omega-3 fatty acids can differentially modulate TNF-α-induced inflammatory stimuli and that caveolae and its fatty acid composition play a regulatory role during TNF-α-induced endothelial cell activation and inflammation.

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Section: Introductionmentioning

confidence: 99%

The role of fatty acids and caveolin-1 in tumor necrosis factor α–induced endothelial cell activation

et al. 2008

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“…In the plasma membrane, COX-2 and caveolin-3 (Cav-3) are co-localized in caveolae, a microdomain in which glycosylphosphatidylinositol (GPI)-anchored proteins reside and form a caveolar protein-protein complex in human fibroblasts 64 and in primary cultures of rat chondrocytes. 65 This suggests that the caveolins might play a role in the regulation of COX-2 functions. 65 Type IIA secretory phospholipase A 2 (sPLA 2 -IIA) is present in caveolae and also in the perinuclear area in proximity to COX-2.…”

Section: Functions Of Nuclear Cox-2 and Protein Complexingmentioning

confidence: 99%

“…65 This suggests that the caveolins might play a role in the regulation of COX-2 functions. 65 Type IIA secretory phospholipase A 2 (sPLA 2 -IIA) is present in caveolae and also in the perinuclear area in proximity to COX-2. A GPI-anchored heparan sulfate proteoglycan glypican facilitates the trafficking of sPLA 2 -IIA into particular subcellular compartments, and arachidonic acid thus released from the compartments may link efficiently to the downstream COX-2-mediated PG biosynthesis.…”

Section: Functions Of Nuclear Cox-2 and Protein Complexingmentioning

confidence: 99%

The pro-apoptotic action of stilbene-induced COX-2 in cancer cells: Convergence with the anti-apoptotic effect of thyroid hormone

Lin¹,

Davis

Tang³

et al. 2009

Cell Cycle

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Constitutively expressed cyclooxygenase-2 (COX-2) is a marker of tumor cell aggressiveness. Inducible COX-2 has also been described in cancer cells and localizes in the cancer cell nucleus, where formation of a complex of mitogen-activated protein kinase (MAPK) and COX-2 is antecedent to p53-dependent apoptosis. The stilbene resveratrol is a model pharmacologic activator of this pro-apoptotic mechanism. Physiological concentrations of thyroid hormone are anti-apoptotic in several types of tumor cells. A mechanism by which the hormone is anti-apoptotic is disruption of the nuclear MAPK-COX-2 complex. We review here the apoptosis-relevant effects of resveratrol and thyroid hormone and then speculate about the significance of convergence of these actions in cancer cells in the intact organism. Clinical activity of resveratrol may be modulated by normal tissue levels of endogenous thyroid hormone, and hypothyroidism in the cancer patient -- whether spontaneous or induced by chemotherapeutic agents -- may permit full expression of the apoptotic activity of the administered stilbene. Chronic pharmacologic inhibition of COX-2 may oppose the pro-apoptotic effect of resveratrol.

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“…There is evidence that fatty acids can alter localization and function of caveolae-associated signaling proteins in mouse colonic mucosa [16]. Caveolins also have been reported to co-localize with cyclooxyenase, suggesting that caveolins play a role in regulating the function of this enzyme [17,18]. Besides their role in cellular uptake of lipophilic substances, caveolae house an array of cell signaling molecules involved in endothelial cell dysfunction and inflammation [13].…”

Section: Introductionmentioning

confidence: 99%

Role of Caveolin-1 in Egcg-Mediated Protection Against Linoleic Acid-Induced Endothelial Cell Activation

Hennig¹,

Zheng²,

Smart³

et al. 2008

Atherosclerosis Supplements

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Evidence for Cyclooxygenase-2 Association with Caveolin-3 in Primary Cultured Rat Chondrocytes

Cited by 9 publications

References 30 publications

The role of fatty acids and caveolin-1 in tumor necrosis factor α–induced endothelial cell activation

The role of fatty acids and caveolin-1 in tumor necrosis factor α–induced endothelial cell activation

The pro-apoptotic action of stilbene-induced COX-2 in cancer cells: Convergence with the anti-apoptotic effect of thyroid hormone

Role of Caveolin-1 in Egcg-Mediated Protection Against Linoleic Acid-Induced Endothelial Cell Activation

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