Transcriptional Regulation of Endothelial Nitric-oxide Synthase by Lysophosphatidylcholine

Cieslik, Katarzyna A.; Zembowicz, Artur; Tang, Jih-Lu; Wu, Kenneth K.

doi:10.1074/jbc.273.24.14885

Cited by 76 publications

(71 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The association of decreases in Sp1 binding with promoter activation at first seemed paradoxical. However, other investigators have shown that, in contrast to its accepted role as a homeostatic transactivator (14,15), Sp1 binding can sometimes function as a gene repressor (16,17). Our results demonstrate that the proximal Sp1 binding site in the TNF-␣ promoter can function as a repressor element.…”

Section: Functional Analysis Of Sp1 Binding Sites In a Heterologousmentioning

confidence: 44%

“…Similar to CRE-binding proteins, cAMP-dependent protein kinase (PKA) phosphorylation of Sp1 has been shown to enhance its DNA binding activity (13). Although Sp1 binding can activate transcription (14,15), for some genes Sp1 functions as a repressor (16,17). The promoter motifs or cell characteristics that determine these divergent effects of Sp1 binding are not fully understood.…”

mentioning

confidence: 99%

See 1 more Smart Citation

A Sp1 Binding Site of the Tumor Necrosis Factor α Promoter Functions as a Nitric Oxide Response Element

Wang

Wesley

et al. 1999

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

Section: Functional Analysis Of Sp1 Binding Sites In a Heterologousmentioning

confidence: 44%

mentioning

confidence: 99%

A Sp1 Binding Site of the Tumor Necrosis Factor α Promoter Functions as a Nitric Oxide Response Element

Wang

Wesley

et al. 1999

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…Treatment of endothelial cells with lysoPC resulted in an increased transcription of the e-NOS mRNA in these cells, followed by an increased amount of protein and the corresponding activity. The time span needed for this response (33,34,18) in the case of injected saliva would preclude a significant role of lysoPC regarding the increase in local NO levels, because the feeding of R. prolixus is successfully accomplished in a few minutes (35). Perhaps in ticks, which remain attached to the host on the same site for a greater period, this role of lysoPC would be more noticeable.…”

Section: Discussionmentioning

confidence: 99%

Lysophosphatidylcholine Acts as an Anti-hemostatic Molecule in the Saliva of the Blood-sucking Bug Rhodnius prolixus

Golodne

Monteiro

Graça-Souza

et al. 2003

Journal of Biological Chemistry

View full text Add to dashboard Cite

Blood-sucking arthropods possess a variety of antihemostatic factors in their salivary glands to maintain blood fluidity during feeding. In this work we demonstrate the anti-hemostatic properties of lysophosphatidylcholine (lysoPC) isolated from the salivary glands of Rhodnius prolixus. First, we examined salivary glands of fourth and fifth instar nymphs for their phospholipid composition. The lumen displayed an accumulation of its phospholipid content, mainly phosphatidylcholine and lysoPC, with a 6-fold increase for the latter. To determine the presence of phospholipids in the saliva, fourth instar nymphs were fed with a 32 P-enriched blood meal. After 28 days their saliva was collected and subjected to lipid extraction, thin-layer chromatography, and autoradiography. The results showed the presence in the saliva of the same phospholipids present in the lumen. We then examined possible biological roles of these phospholipids when compared with other known effects of lysoPC. The luminal lipid extract and purified lysoPC from the lumen and saliva were tested for inhibition of washed rabbit platelets' aggregation induced by ␣-thrombin and platelet-activating factor. Both the luminal lipid extract and salivary lysoPC showed an increasing inhibition of aggregation, which correlated with the response of the platelets to standard lysoPC (up to 13 g/ml). Next, salivary lysoPC was incubated with porcine arterial endothelial cells for 24 h. After incubation, culture medium was assayed for nitric oxide and showed increased nitric oxide production, similar to control cells exposed to standard lysoPC (up to 20 g/ ml). Together these data demonstrate the presence of lysoPC in the saliva of Rhodnius prolixus and its potential anti-hemostatic activities.Hematophagous arthropods rely on a wide array of antihemostatic substances to counteract vertebrate responses to blood loss and to obtain their blood meal successfully (1). These salivary compounds show distinct properties and are generally involved with inhibition of coagulation, platelet aggregation, and vasoconstriction (2). These molecules include peptides such as tachykinins (3), maxadilan (4), nitric oxide (NO) 1 -binding proteins such as nitrophorins (5), and prostaglandins (6). The small lesions elicited by the mouthparts of the arthropod most likely evoke platelet aggregation and vasoconstriction by the vertebrate host. Therefore, the formation of the platelet plug is specifically inhibited by collagen inhibitors, apyrases, catechol oxidases, thrombin inhibitors, NO-releasing proteins, fibrinogen receptor agonists, and a specific platelet aggregation inhibitor (7,8). The complexity of anti-hemostatic mechanisms has recently been addressed with the use of proteomic techniques (9, 10). Hundreds of gene sequences were obtained, and most of them await future tests concerning the anti-hemostatic properties of the proteins they code for.Lysophosphatidylcholine (lysoPC) is a component of oxidized low-density lipoprotein, which is involved in the pathogenesis of atheroscleros...

show abstract

“…Subsequently, Li et al (12) have reported that HDL binding to SR-BI activates eNOS in transfected Chinese hamster ovary (CHO) cells in an Akt-independent manner, possibly involving ceramide, whereas Mineo et al (13) reported that HDL caused eNOS activation through phosphorylation at Ser-1179 in both endothelial cells and COS M6 cells transfected with eNOS. Regulation of eNOS activity by phosphorylation is complex and involves an intricate interaction between multiple sites (Ser-116, Thr-497, Ser-617, Ser-635, and Ser-1179) and the activities of numerous kinases and phosphatases, including AMP activated protein kinase (AMPK) (14), PKA (15), Akt͞PKB (16), PKC (17), PP1 (18), and PP2A (19). In the current study, activation of eNOS was characterized by studying five phosphorylation sites within the eNOS enzyme.…”

mentioning

confidence: 99%

High-density lipoprotein and apolipoprotein AI increase endothelial NO synthase activity by protein association and multisite phosphorylation

Drew

Fidge

Gallon-Beaumier

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

156

105

View full text Add to dashboard Cite

NO propagates a number of antiatherogenic effects in the endothelium, and diminished availability has been associated with vascular disease. Recently it has been reported that phosphorylation of endothelial NO synthase (eNOS) at Ser-1179 is required to increase activity in response to stimuli, including high-density lipoprotein (HDL). The current study was undertaken to further examine the mechanism by which HDL activates eNOS and to specifically determine the role of the major apolipoprotein of HDL, apolipoprotein AI (ApoAI). Phosphorylation of eNOS residues Ser-116, Ser-617, Ser-635, Ser-1179, and Thr-497 after incubation with ApoAI and HDL was examined. There were significant increases in phosphorylation at Ser-116 in response to both HDL and ApoAI and similar magnitudes of dephosphorylation at Thr-497. Ser-1179 phosphorylation increased transiently but returned to basal level after 2.5 min. Data demonstrating activation of AMP activated protein kinase (AMPK) during HDL and ApoAI incubation suggests that AMPK may play a role in activation of eNOS. NO release in response to HDL and ApoAI stimulation in endothelial cells paralleled the time frames of phosphorylation, suggesting a causal relationship. Furthermore, ApoAI was found to associate with eNOS in endothelial cells and bind transfected eNOS in Chinese hamster ovary cells, whereas confocal data demonstrates colocalization of ApoAI and eNOS in the perinuclear region, suggesting a protein-protein interaction. Collectively, the results indicate that HDL and ApoAI increase eNOS activity by multisite phosphorylation changes, involving AMPK activation after protein association between ApoAI and eNOS. D ecreased bioavailability of endothelium-derived NO is an important antecedent to atherosclerosis (1). NO inhibits events that promote atherosclerotic progression, including vasoconstriction, monocyte adhesion, and smooth muscle cell proliferation (2). The bulk of endothelium-derived NO is generated from L-arginine conversion by endothelial NO synthase (eNOS, NOS III) (3). Activity of eNOS is modulated by complex mechanisms including phosphorylation, protein-protein interactions, substrate availability, and intracellular Ca 2ϩ flux. Numerous biological agents have been associated with changes in eNOS activity, including caveolin (4), Ca 2ϩ calmodulin (5), HSP90 (6), Dynamin-2 (7), bradykinin (8), and more recently high-density lipoprotein (HDL) (9). HDL plays a major role in reversing and preventing progression of vascular disease through its role in reverse cholesterol transport and its involvement in signaling͞receptor pathways of cholesterol metabolism (10). Possibly, some cardiovascular protective effects of HDL are mediated via activation of eNOS, although the precise nature of this interaction remains unclear. The current study was undertaken to examine the mechanism by which HDL activates eNOS and to determine whether the major apolipoprotein of HDL, apolipoprotein AI (ApoAI), mediates the response.Endothelial cells incubated with HDL exhibit an increase in...

show abstract

Transcriptional Regulation of Endothelial Nitric-oxide Synthase by Lysophosphatidylcholine

Cited by 76 publications

References 33 publications

A Sp1 Binding Site of the Tumor Necrosis Factor α Promoter Functions as a Nitric Oxide Response Element

A Sp1 Binding Site of the Tumor Necrosis Factor α Promoter Functions as a Nitric Oxide Response Element

Lysophosphatidylcholine Acts as an Anti-hemostatic Molecule in the Saliva of the Blood-sucking Bug Rhodnius prolixus

High-density lipoprotein and apolipoprotein AI increase endothelial NO synthase activity by protein association and multisite phosphorylation

Contact Info

Product

Resources

About