Phosphatidic acid as a second messenger in human polymorphonuclear leukocytes. Effects on activation of NADPH oxidase.

Agwu, David E.; McPhail, Linda C.; Sozzani, Silvano; Bass, David; McCall, Charles E.

doi:10.1172/jci115336

Cited by 161 publications

(60 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Taken together, the present results strongly suggest that high glucose level stimulated ROS production through PKC-dependent activation of NAD(P)H oxidase in cultured vascular cells. Although PKC inhibitor normalized the increased ROS production induced by high glucose level statistically completely, it should be stated that phosphatidic acid also can stimulate NADPH oxidase (50,51). Because phosphatidic acid is an intermediate of de novo DAG synthesis, its level should be increased by high glucose level.…”

Section: Resultsmentioning

confidence: 99%

High glucose level and free fatty acid stimulate reactive oxygen species production through protein kinase C--dependent activation of NAD(P)H oxidase in cultured vascular cells.

et al. 2000

View full text Add to dashboard Cite

Recent studies have revealed that vascular cells can produce reactive oxygen species (ROS) through NAD(P)H oxidase, which may be involved in vascular injury. However, the pathological role of vascular NAD(P)H oxidase in diabetes or in the insulin-resistant state remains unknown. In this study, we examined the effect of high glucose level and free fatty acid (FFA) (palmitate) on ROS production in cultured aortic smooth muscle cells (SMCs) and endothelial cells (ECs) using electron spin resonance spectroscopy. Exposure of cultured SMCs or ECs to a high glucose level (400 mg/dl) for 72 h significantly increased the free radical production compared with low glucose level exposure (100 mg/dl). Treatment of the cells for 3 h with phorbol myristic acid (PMA), a protein kinase C (PKC) activator, also increased free radical production. This increase was restored to the control value by diphenylene iodonium, a NAD(P)H oxidase inhibitor, suggesting ROS production through PKC-dependent activation of NAD(P)H oxidase. The increase in free radical production by high glucose level exposure was completely restored by both diphenylene iodonium and GF109203X, a PKC-specific inhibitor. Exposure to palmitate (200 µmol/l) also increased free radical production, which was concomitant with increases in diacylglycerol level and PKC activity. Again, this increase was restored to the control value by both diphenylene iodonium and GF109203X. The present results suggest that both high glucose level and palmitate may stimulate ROS production through PKC-dependent activation of NAD(P)H oxidase in both vascular SMCs and ECs. This finding may be involved in the excessive acceleration of atherosclerosis in patients with diabetes and insulin resistance syndrome.

show abstract

Section: Resultsmentioning

confidence: 99%

High glucose level and free fatty acid stimulate reactive oxygen species production through protein kinase C--dependent activation of NAD(P)H oxidase in cultured vascular cells.

et al. 2000

View full text Add to dashboard Cite

show abstract

“…The small molecule inhibitors also protected mice from lipopolysaccharide-mediated endotoxic shock and from lung injury in a model of hemorrhage and resuscitation (36). Others have demonstrated that formyl peptide-stimulated neutrophils can be induced to produce PA by a phospholipase D-dependent mechanism (17). In this setting, the PA activated NADPH oxidase.…”

Section: Discussionmentioning

confidence: 99%

“…Additionally, Fourcade et al (16) have demonstrated that a secretory phospholipase A 2 acts upon membrane microvesicles shed from activated cells to convert PA to LPA. PA is a key intermediate in membrane phospholipid biosynthesis (10), but it can also serve as a second messenger in activated cells (17). PA can be converted to CDP-diacylglycerol or to diacylglycerol by the action of PA phosphatase or to LPA by the phospholipase A 2 .…”

mentioning

confidence: 99%

Human Lysophosphatidic Acid Acyltransferase

Eberhardt

Gray

Tjoelker

1997

Journal of Biological Chemistry

114

View full text Add to dashboard Cite

Lysophosphatidic acid (1-acyl-sn-glycero-3-phosphate (LPA)) is a phospholipid with diverse biological activities. The mediator serves as an intermediate in membrane phospholipid metabolism but is also produced in acute settings by activated platelets. LPA is converted to phosphatidic acid, itself a lipid mediator, by an LPA acyltransferase (LPAAT). A human expressed sequence tag was identified by homology with a coconut LPAAT and used to isolate a full-length human cDNA from a heart muscle library. The predicted amino acid sequence bears 33% identity with a Caenorhabditis elegans LPAAT homologue and 23-28% identity with plant and prokaryotic LPAATs. Recombinant protein produced in COS 7 cells exhibited LPAAT activity with a preference for LPA as the acceptor phosphoglycerol and arachidonyl coenzyme A as the acyl donor. Northern blotting demonstrated that the mRNA is expressed in most human tissues including a panel of brain subregions; expression is highest in liver and pancreas and lowest in placenta. The human LPAAT gene is contained on six exons that map to chromosome 9, region q34.3.

show abstract

“…As RelA/p65 is replaced at the TNF-␣ promoter in tolerant THP-1 cells by dimer exchange with RelB (23), we asked whether SIRT1 interacts with the multicomponent repressor complex proteins RelB and heterochromatin linker histone H1 (8,11,24,25). Our previous work showed that RelB promoter recruitment directs facultative heterochromatin formation by first binding to G9a methyltransferase, which methylates H3K9; other members of chromatin modifiers include histone linker H1, heterochromatin protein 1, and DNA CpG methyltransferases DNMT 3a/3b (11,13,25).…”

Section: Sirt1 Remains Bound To Tnf-␣ Promoter During Endotoxin Tolermentioning

confidence: 99%

NAD+-dependent SIRT1 Deacetylase Participates in Epigenetic Reprogramming during Endotoxin Tolerance

Liu

Yoza

Gazzar

et al. 2011

Journal of Biological Chemistry

226

252

View full text Add to dashboard Cite

Gene-selective epigenetic reprogramming and shifts in cellular bioenergetics develop when Toll-like receptors (TLR) recognize and respond to systemic life-threatening infections. Using a human monocyte cell model of endotoxin tolerance and human leukocytes from acute systemic inflammation with sepsis, we report that energy sensor sirtuin 1 (SIRT1) coordinates the epigenetic and bioenergy shifts. After TLR4 signaling, SIRT1 rapidly accumulated at the promoters of TNF-␣ and IL-1␤, but not IB␣; SIRT1 promoter binding was dependent on its co-factor, NAD ؉ . During this initial process, SIRT1 deacetylated RelA/ p65 lysine 310 and nucleosomal histone H4 lysine 16 to promote termination of NFB-dependent transcription. SIRT1 then remained promoter bound and recruited de novo induced RelB, which directed assembly of the mature transcription repressor complex that generates endotoxin tolerance. SIRT1 also promoted de novo expression of RelB. During sustained endotoxin tolerance, nicotinamide phosphoribosyltransferase (Nampt), the rate-limiting enzyme for endogenous production of NAD ؉ , and SIRT1 expression increased. The elevation of SIRT1 required protein stabilization and enhanced translation. To support the coordination of bioenergetics in human sepsis, we observed elevated NAD ؉ levels concomitant with SIRT1 and RelB accumulation at the TNF-␣ promoter of endotoxin tolerant sepsis blood leukocytes. We conclude that TLR4 stimulation and human sepsis activate pathways that couple NAD ؉ and its sensor SIRT1 with epigenetic reprogramming.Two cellular processes predictably accompany TLR-mediated acute systemic inflammation caused by sepsis, a highly destructive and often lethal process. The first process occurs when epigenetic alterations reprogram distinct functional sets of genes to both activate and repress transcription of hundreds of genes (1, 2); this transcriptome reprogramming generates the phenomenon known as endotoxin tolerance (3). Endotoxin tolerance requires TLR 3 receptor signaling of NFB master regulator, which first induces and then represses rapid response and potentially autotoxic proinflammatory TNF-␣ and IL-1␤. To control the initial recognition and response phases induced by TLR, gene-specific reprogramming selectively modifies chromatin structure and shifts nucleosomes on responsive euchromatin to form silent heterochromatin at acute proinflammatory genes; in contrast, genes encoding anti-inflammatory and antimicrobial mediators maintain responsive euchromatin (4, 5). This gene set-selective reprogramming generates a clinically relevant phenotypic transition from the hyperinflammatory to the hypoinflammatory endotoxin tolerant state, which may last hours, days, or weeks, depending on the strength of the initial TLR response (4, 5). The physiologic importance of endotoxin tolerance is still incompletely understood, but likely reflects an attempt to recover homeostasis (3).Others and we (6 -9) reported how temporal transitions in epigenetic programming alter the course of acute inflammation. NFB master ...

show abstract

Phosphatidic acid as a second messenger in human polymorphonuclear leukocytes. Effects on activation of NADPH oxidase.

Cited by 161 publications

References 56 publications

High glucose level and free fatty acid stimulate reactive oxygen species production through protein kinase C--dependent activation of NAD(P)H oxidase in cultured vascular cells.

High glucose level and free fatty acid stimulate reactive oxygen species production through protein kinase C--dependent activation of NAD(P)H oxidase in cultured vascular cells.

Human Lysophosphatidic Acid Acyltransferase

NAD+-dependent SIRT1 Deacetylase Participates in Epigenetic Reprogramming during Endotoxin Tolerance

Contact Info

Product

Resources

About