Human haptoglobin: an endogenous inhibitor of prostaglandin synthase

Saeed, Sheikh A.; Denning-Kendall, Patricia A.; McDonald-Gibson, Wendy J.; Collier, H. O. J.

doi:10.1007/978-94-010-9423-8_41

Cited by 5 publications

(5 citation statements)

References 14 publications

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“…Conversely, plasma obtained from hypercholesterolaemic and control rabbits significantly inhibited AA metabolism, which is in agreement with results of previous studies in humans 8,10,11 . In the present study, we investigated whether the more prevalent proteins in plasma may be responsible for the inhibition of AA metabolism.…”

Section: Discussionsupporting

confidence: 91%

“…In previous studies, plasma from subjects with normal cholesterol inhibited AA metabolism, 8–11 rather than enhancing it, which suggests the presence of one or more endogenous substances with a potential for therapeutic effects. The first goal of the present study was to establish the feasibility of using an animal model to determine whether plasma from normal and hypercholesterolaemic rabbits inhibits AA metabolism.…”

Section: Introductionmentioning

confidence: 88%

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Lipoproteins Inhibit Platelet Aggregation and Arachidonic Acid Metabolism in Experimental Hypercholesterolaemia

Aslam

Saeed

Ahmed

et al. 2008

Clin Exp Pharma Physio

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1. Human plasma contains unidentified components that inhibit arachidonic acid (AA) metabolism. In the present study, we investigated whether plasma from rabbits fed a normal or high-cholesterol diet for 16 weeks also inhibits AA metabolism. Specifically, we studied the effects of plasma on platelet aggregation and on the production of AA metabolites, tri-hydroxyeicosatrienoic acid, 12-hydroxyeicosatetraenoic acid and thromboxane B(2). 2. Haematological and lipid profiles were altered by a high-cholesterol diet. Platelets from hypercholesterolaemic rabbits showed enhanced aggregatory sensitivity to AA and platelet-activating factor. However, plasma from hypercholesterolaemic and control rabbits, when added to the incubation mixture, significantly inhibited platelet aggregation and eicosanoid production. 3. High- and low-density lipoprotein (HDL and LDL, respectively) concentrations increased several-fold in plasma with cholesterol feeding. When added directly to the incubation mixture, both HDL and LDL inhibited platelet aggregation, as well as AA metabolism. 4. Haptoglobin, albumin and Cohn's fraction IV, but not globulins, exhibited antiplatelet and anti-AA metabolism activities. Their concentrations in plasma were not affected by cholesterol feeding. 5. We conclude that LDL and HDL account for at least some of the inhibition of AA metabolism produced by plasma.

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 88%

Lipoproteins Inhibit Platelet Aggregation and Arachidonic Acid Metabolism in Experimental Hypercholesterolaemia

Aslam

Saeed

Ahmed

et al. 2008

Clin Exp Pharma Physio

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“…Although relatively less attention has been paid to the physiological (i.e., nonpharmacological) factors suppressing prostanoid synthesis, it appears that prostaglandin generation can be negatively controlled by endogenous systems. Glucocorticoids/ lipocortins have been among the earliest discovered and most thoroughly studied endogenous systems that downregulate the synthesis of prostanoids (36). Inhibitory effects of steroids on the arachidonate cascade may occur by destabilizing the COX-2 transcript (37), and also via inhibiting the activity of phospholipase A 2 , an enzyme responsible for the liberation of AA from cellular membrane phospholipids (38,39).…”

Section: Discussionmentioning

confidence: 99%

11,12-Epoxyeicosatrienoic Acid Attenuates Synthesis of Prostaglandin E₂in Rat Monocytes Stimulated with Lipopolysaccharide

Kozak

Aronoff²,

Boutaud³

et al. 2003

Exp Biol Med (Maywood)

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Cytochrome P-450 monooxygenase (epoxygenase)-derived arachidonic acid (AA) metabolites, including 11,12-epoxyeicosatrienoic acid (11,12-EET), possess anti-inflammatory and antipyretic properties. Prostaglandin E2 (PGE2), a cyclooxygenase (COX)-derived metabolite of AA, is a well-defined mediator of fever and inflammation. We have tested the hypothesis that 11,12-EET attenuates synthesis of PGE2 in monocytes, which are the cells that are indispensable for induction of fever and initiation of inflammation. Monocytes isolated from freshly collected rat blood were stimulated with lipopolysaccharide (LPS; 100 ng/2 x 10(5) cells) to induce COX-2 and stimulate generation of PGE2. SKF-525A, an inhibitor of epoxygenases, significantly augmented the lipopolysaccharide-provoked synthesis of PGE2 in cell culture in a concentration-dependent manner. It did not affect, however, elevation of the expression of COX-2 protein in monocytes stimulated with LPS. 11,12-EET also did not affect the induction of COX-2 in monocytes incubated with lipopolysaccharide. However, 11,12-EET suppressed, in a concentration-dependent fashion, the generation of PGE2 in incubates. Preincubation of a murine COX-2 preparation for 0-5 min with three concentrations of 11,12-EET (1, 5, and 10 microM) inhibited the oxygenation of [14C]-labeled AA by the enzyme. The inhibitory effect of 11,12-EET on COX-2 was time-and-concentration-dependent, suggesting a mechanism-based inhibition. Based on these data, we conclude that 11,12-EET suppresses generation of PGE2 in monocytes via modulating the activity of COX-2. These data support the hypothesis that epoxygenase-derived AA metabolites constitute a negative feedback on the enhanced synthesis of prostaglandins upon inflammation.

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“…Haptoglobin (Hp) is a well-characterized glycoprotein found in all mammals but also, in its simpler form, in fish. However, its exact physiological function is still uncertain [ 37 ]. Hp functions as an antioxidant to prevent oxidative damage to tissues, including the kidney [ 38 ].…”

Section: Known Roles Of Major Acute-phase Proteins Detected By Ngs In...mentioning

confidence: 99%

“…Hp functions as an antioxidant to prevent oxidative damage to tissues, including the kidney [ 38 ]. Further, already-described Hp functions include pro-angiogenic [ 39 ] and immunomodulatory [ 40 ] functions through inhibition of cathepsin-B [ 41 ] and prostaglandin synthase [ 37 ]. Moreover, especially haptoglobin but also fibrinogen beta were indicative of metastasis in a human triple-negative MDA-MB-231 breast cancer model [ 42 ].…”

Section: Known Roles Of Major Acute-phase Proteins Detected By Ngs In...mentioning

confidence: 99%

A New Role of Acute Phase Proteins: Local Production Is an Ancient, General Stress-Response System of Mammalian Cells

Hamar

2022

IJMS

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The prevailing general view of acute-phase proteins (APPs) is that they are produced by the liver in response to the stress of the body as part of a systemic acute-phase response. We demonstrated a coordinated, local production of these proteins upon cell stress by the stressed cells. The local, stress-induced APP production has been demonstrated in different tissues (kidney, breast cancer) and with different stressors (hypoxia, fibrosis and electromagnetic heat). Thus, this local acute-phase response (APR) seems to be a universal mechanism. APP production is an ancient defense mechanism observed in nematodes and fruit flies as well. Local APP production at the tissue level is also supported by sporadic literature data for single proteins; however, the complex, coordinated, local appearance of this stress response has been first demonstrated only recently. Although a number of literature data are available for the local production of single acute-phase proteins, their interpretation as a local, coordinated stress response is new. A better understanding of the role of APPs in cellular stress response may also be of diagnostic/prognostic and therapeutic significance.

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Human haptoglobin: an endogenous inhibitor of prostaglandin synthase

Cited by 5 publications

References 14 publications

Lipoproteins Inhibit Platelet Aggregation and Arachidonic Acid Metabolism in Experimental Hypercholesterolaemia

Lipoproteins Inhibit Platelet Aggregation and Arachidonic Acid Metabolism in Experimental Hypercholesterolaemia

11,12-Epoxyeicosatrienoic Acid Attenuates Synthesis of Prostaglandin E₂in Rat Monocytes Stimulated with Lipopolysaccharide

A New Role of Acute Phase Proteins: Local Production Is an Ancient, General Stress-Response System of Mammalian Cells

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Human haptoglobin: an endogenous inhibitor of prostaglandin synthase

Cited by 5 publications

References 14 publications

Lipoproteins Inhibit Platelet Aggregation and Arachidonic Acid Metabolism in Experimental Hypercholesterolaemia

Lipoproteins Inhibit Platelet Aggregation and Arachidonic Acid Metabolism in Experimental Hypercholesterolaemia

11,12-Epoxyeicosatrienoic Acid Attenuates Synthesis of Prostaglandin E2in Rat Monocytes Stimulated with Lipopolysaccharide

A New Role of Acute Phase Proteins: Local Production Is an Ancient, General Stress-Response System of Mammalian Cells

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Product

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11,12-Epoxyeicosatrienoic Acid Attenuates Synthesis of Prostaglandin E₂in Rat Monocytes Stimulated with Lipopolysaccharide