Human apolipoprotein A-I induces cyclooxygenase-2 expression and prostaglandin I-2 release in endothelial cells through ATP-binding cassette transporter A1

2011 ◽  
Vol 301 (3) ◽  
pp. C739-C748 ◽  
Author(s):  
Donghui Liu ◽  
Liang Ji ◽  
Xunliang Tong ◽  
Bing Pan ◽  
Jing-Yan Han ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Umbilical Vein ◽  
Cyclooxygenase 2 ◽  
Mitogen Activated Protein Kinase ◽  
Atp Binding ◽  
Dependent Manner ◽  
Atp Binding Cassette Transporter ◽  
Apolipoprotein A ◽  
Cox 2 ◽  
Atp Binding Cassette

High-density lipoprotein (HDL) can induce cyclooxygenase-2 (COX-2) expression and prostacyclin I-2 (PGI-2) release in endothelial cells to exert multiple antiatherogenic functions. This effect has been attributed mainly to the role of sphingosine-1-phosphate (S1P) integrated in HDL. However, whether apolipoprotein A-I (apoA-I), the major apolipoprotein of HDL, could induce COX-2 expression and PGI-2 release still remains unclear. In the present study, we selectively delipidated HDL and confirmed that apoA-I could facilitate COX-2 expression and PGI-2 production in human umbilical vein endothelial cells (HUVECs). ApoA-I, but not trypsinized apoA-I, induced COX-2 expression in a time- and dose-dependent manner consistent with a key role for apoA-I in this process. Additionally, cotreatment of apoA-I with S1P further enhanced COX-2 expression and PGI-2 production in HUVECs. These effects triggered by apoA-I were not inhibited by pertussis toxin, consistent with SIP receptor independent pathway for apoA-I effect. Moreover, we demonstrated that the activation of p38 mitogen-activated protein kinase (MAPK), extracellular receptor kinase (ERK) 1/2, and JAK2 pathways by apoA-I was involved in the expression of COX-2 and the release of PGI-2 in HUVECs, and these effects were inhibited by their specific inhibitors, respectively. Small interfering RNA experiments showed that ATP binding-cassette transporter A1 (ABCA1) was required for COX-2 expression and PGI-2 release induced by apoA-I. Thus our results indicate that apoA-I induces COX-2 expression and PGI-2 release through ABCA1 and the activation of intracellular p38 MAPK, ERK1/2, as well as JAK2 pathways, and apoA-I can reinforce these effects with S1P in HUVECs. These novel effects of apoA-I could in part mediate antiatherogenic effects of HDL.

scholarly journals Cyclooxygenase-2 Glycosylation Is Affected by Peroxynitrite in Endothelial Cells: Impact on Enzyme Activity and Degradation

Antioxidants ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 496
Author(s):  
Sonia Eligini ◽  
Susanna Colli ◽  
Aida Habib ◽  
Giancarlo Aldini ◽  
Alessandra Altomare ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
De Novo ◽  
Cyclooxygenase 2 ◽  
Nitric Oxide Donors ◽  
Metabolic Labeling ◽  
Dependent Manner ◽  
De Novo Synthesis ◽  
Human Endothelial Cells ◽  
Prolonged Incubation ◽  
Cox 2

The exposure of human endothelial cells to 3-morpholinosydnonimine (SIN-1) induced the expression of cyclooxygenase-2 (COX-2) in a dose- and time-dependent manner. Interestingly, after a prolonged incubation (>8 h) several proteoforms were visualized by Western blot, corresponding to different states of glycosylation of the protein. This effect was specific for SIN-1 that generates peroxynitrite and it was not detected with other nitric oxide-donors. Metabolic labeling experiments using 35S or cycloheximide suggested that the formation of hypoglycosylated COX-2 was dependent on de novo synthesis of the protein rather than the deglycosylation of the native protein. Moreover, SIN-1 reduced the activity of the hexokinase, the enzyme responsible for the first step of glycolysis. The hypoglycosylated COX-2 induced by SIN-1 showed a reduced capacity to generate prostaglandins and the activity was only partially recovered after immunoprecipitation. Finally, hypoglycosylated COX-2 showed a more rapid rate of degradation compared to COX-2 induced by IL-1α and an alteration in the localization with an accumulation mainly detected in the nuclear membrane. Our results have important implication to understand the effect of peroxynitrite on COX-2 expression and activity, and they may help to identify new pharmacological tools direct to increase COX-2 degradation or to inhibit its activity.

Intracisternal administration of transforming growth factor-β evokes fever through the induction of cyclooxygenase-2 in brain endothelial cells

2008 ◽  
Vol 294 (1) ◽  
pp. R266-R275 ◽  
Author(s):  
Shigenobu Matsumura ◽  
Tetsuro Shibakusa ◽  
Teppei Fujikawa ◽  
Hiroyuki Yamada ◽  
Kiyoshi Matsumura ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Growth Factor ◽  
Proinflammatory Cytokines ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Cyclooxygenase 2 ◽  
Dependent Manner ◽  
Cox 2 ◽  
Β Receptor

Transforming growth factor-β (TGF-β), a pleiotropic cytokine, regulates cell proliferation, differentiation, and apoptosis, and plays a key role in development and tissue homeostasis. TGF-β functions as an anti-inflammatory cytokine because it suppresses microglia and B-lymphocyte functions, as well as the production of proinflammatory cytokines. However, we previously demonstrated that the intracisternal administration of TGF-β induces fever like that produced by proinflammatory cytokines. In this study, we investigated the mechanism of TGF-β-induced fever. The intracisternal administration of TGF-β increased body temperature in a dose-dependent manner. Pretreatment with cyclooxygenase-2 (COX-2)-selective inhibitor significantly suppressed TGF-β-induced fever. COX-2 is known as one of the rate-limiting enzymes of the PGE2 synthesis pathway, suggesting that fever induced by TGF-β is COX-2 and PGE2 dependent. TGF-β increased PGE2 levels in cerebrospinal fluid and increased the expression of COX-2 in the brain. Double immunostaining of COX-2 and von Willebrand factor (vWF, an endothelial cell marker) revealed that COX-2-expressing cells were mainly endothelial cells. Although not all COX-2-immunoreactive cells express TGF-β receptor, some COX-2-immunoreactive cells express activin receptor-like kinase-1 (ALK-1, an endothelial cell-specific TGF-β receptor), suggesting that TGF-β directly or indirectly acts on endothelial cells to induce COX-2 expression. These findings suggest a novel function of TGF-β as a proinflammatory cytokine in the central nervous system.

scholarly journals The Role of Apolipoprotein A-I Helix 10 in Apolipoprotein-mediated Cholesterol Efflux via the ATP-binding Cassette Transporter ABCA1

2002 ◽  
Vol 277 (42) ◽  
pp. 39477-39484 ◽  
Author(s):  
Stacey E. Panagotopulos ◽  
Scott R. Witting ◽  
Erica M. Horace ◽  
David Y. Hui ◽  
J. Nicholas Maiorano ◽  
...  
Keyword(s):  
Cholesterol Efflux ◽  
Atp Binding ◽  
Atp Binding Cassette Transporter ◽  
Apolipoprotein A ◽  
Atp Binding Cassette

Effect of Apolipoprotein A-I on ATP Binding Cassette Transporter A1 Degradation and Cholesterol Efflux in THP-1 Macrophage-derived Foam Cells

2004 ◽  
Vol 36 (3) ◽  
pp. 218-226 ◽  
Author(s):  
Chao-Ke Tang ◽  
Guo-Hua Tang ◽  
Guang-Hui Yi ◽  
Zuo Wang ◽  
Lu-Shan Liu ◽  
...  
Keyword(s):  
Protease Inhibitors ◽  
Cholesterol Efflux ◽  
Foam Cells ◽  
Atp Binding ◽  
Thiol Protease ◽  
Atp Binding Cassette Transporter ◽  
Apolipoprotein A ◽  
Abca1 Protein ◽  
Abca1 Mrna ◽  
Atp Binding Cassette

Abstract Cholesterol-loaded macrophage foam cells are a central component of atherosclerotic lesions. ATP binding cassette transporter A1 (ABCA1), the defective molecule in Tangier disease, mediates the efflux of phospholipid and cholesterol from cells to apolipoprotein A-I (apoA-I), reversing foam cell formation. This study investigated the effect of apoA-I on ABCA1 degradation and cholesterol efflux in THP-1 macrophage-derived foam cells. After exposure of the cultured THP-1 macrophage-derived foam cells to apoA-I for different time, cholesterol efflux, ABCA1 mRNA and protein levels were determined by FJ-2107P type liquid scintillator, RT-PCR and Western blot, respectively. The mean ABCA1 fluorescence intensity on THP-1 macrophage-derived foam cells was detected by flow cytometry. Results showed that apoA-I markedly increased ABCA1-mediated cholesterol efflux from THP-1 macrophage-derived foam cells. This was accompanied by an increase in the content of ABCA1. ApoA-I did not alter ABCA1 mRNA abundance. Significantly, thiol protease inhibitors increased the level of ABCA1 protein and slowed its decay in THP-1 macrophage-derived foam cells, whereas none of the proteosome-specific inhibitor lactacystin, other protease inhibitors, or the lysosomal inhibitor NH4Cl showed such effects. The apoA-I-mediated cellular cholesterol efflux was enhanced by thiol protease inhibitors. Our results suggested that thiol protease inhibitors might provide an alternative way to upregulate ABCA1 protein. This strategy is especially appealing since it may mimic the stabilizing effect of the natural ligands apoA-I.

scholarly journals ATP-binding Cassette Transporter A7 (ABCA7) Binds Apolipoprotein A-I and Mediates Cellular Phospholipid but Not Cholesterol Efflux

2003 ◽  
Vol 278 (44) ◽  
pp. 42906-42912 ◽  
Author(s):  
Nan Wang ◽  
Debin Lan ◽  
Marie Gerbod-Giannone ◽  
Patrick Linsel-Nitschke ◽  
Andreas Werner Jehle ◽  
...  
Keyword(s):  
Cholesterol Efflux ◽  
Atp Binding ◽  
Atp Binding Cassette Transporter ◽  
Apolipoprotein A ◽  
Cellular Phospholipid ◽  
Atp Binding Cassette

scholarly journals The Induction of Cyclooxygenase-2 in IL-1β-Treated Endothelial Cells is Inhibited by Prostaglandin E2 through cAMP

1999 ◽  
Vol 8 (6) ◽  
pp. 287-294 ◽  
Author(s):  
Pravit Akarasereenont ◽  
Kitirat Techatrisak ◽  
Sirikul Chotewuttakorn ◽  
Athiwat Thaworn
Keyword(s):  
Endothelial Cells ◽  
Biological Activities ◽  
Umbilical Vein ◽  
The Body ◽  
Prostaglandin E ◽  
Dependent Manner ◽  
Negative Feedback Regulation ◽  
Cox 2 ◽  
Arachidonic Acids ◽  
Cox 1

Prostaglandins (PGS) have numerous cardiovascular and inflammatory effects. Cyclooxygenase (COX), which exists as COX-1 and COX-2 isoforms, is the first enzyme in the pathway in which arachidonic acid is converted to PGs. Prostaglandin E2 (PGE2) exerts a variety of biological activities for the maintenance of local homeostasis in the body. Elucidation of PGE2 involvement in the signalling molecules such as COX could lead to potential therapeutic interventions. Here, we have investigated the effects of PGE2 on the induction of COX-2 in human umbilical vein endothelial cells (HUVEC) treated with interleukin-1β (IL-1β 1 ng/ml). COX activity was measured by the production of 6-keto-PGF1α, PGE2, PGF2α and thromboxane B2 (TXB2) in the presence of exogenous arachidonic acids (10 μM for 10 min) using enzyme immunoassay (EIA). COX-1 and COX-2 protein was measured by immunoblotting using specific antibody. Untreated HUVEC contained only COX-1 protein while IL-1β treated HUVEC contained COX-1 and COX-2 protein. PGE2 (3 μM for 24 h) did not affect on COX activity and protein in untreated HUVEC. Interestingly, PGE2 (3 μM for 24 h) can inhibit COX-2 protein, but not COX-1 protein, expressed in HUVEC treated with IL1 β. This inhibition was reversed by coincubation with forskolin (100 μM). The increased COX activity in HUVEC treated with IL-1β was also inhibited by PGE2 (0.03, 0.3 and 3 μM for 24 h) in a dose-dependent manner. Similarly, forskolin (10, 50 or 100 μM) can also reverse the inhibition of PGE2 on increased COX activity in IL-1β treated HUVEC. The results suggested that (i) PGE2 can initiate negative feedback regulation in the induction of COX-2 elicited by IL-1β in endothelial cells, (ii) the inhibition of PGE2 on COX-2 protein and activity in IL-1β treated HUVEC is mediated by cAMP and (iii) the therapeutic use of PGE2 in the condition which COX-2 has been involved may have different roles.

Sign in / Sign up

Export Citation Format

Share Document