Dual inhibition of cyclooxygenase and lipoxygenase by human haptoglobin: Its polymorphism and relation to hemoglobin binding

Saeed, Sheikh A.; Ahmad, Nabeel; Ahmed, Sagheer

doi:10.1016/j.bbrc.2006.12.092

Cited by 49 publications

(44 citation statements)

References 21 publications

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“…However, haptoglobin is known to be more potent inhibitor of prostaglandin synthesis than albumin [9]. The IC 50 of pure haptoglobin against prostaglandin synthesis is about 100 µg [5] while in the current study human plasma displayed IC 50 of 0.5% against prostaglandin synthesis which corresponds to about 50µg of haptoglobin. This indicates that constituents of plasma other than haptoglobin are also involved, including albumin as stated above.…”

Section: Resultsmentioning

confidence: 51%

“…While albumin is found in all mammals and has been shown to possess inhibitory activities against AA metabolism and platelet aggregation in human, studies show it is only partly responsible for these effects of plasma [9,17]. Previous work from our group has shown that human haptoglobin also possesses significant inhibitory activity against AA metabolism and platelet aggregation [5,8,9,[15][16][17]. In healthy individuals, the albumin concentration in plasma is around 35-55 mg/mL [18] while the concentration of haptoglobin is roughly 100-times lower than that of albumin [19].…”

Section: Resultsmentioning

confidence: 99%

“…The homogenate was again centrifuged at 1200 g for twenty minutes. After centrifugation, the supernatant was isolated and incubated with 10 µg unlabeled AA and 0.1 µCi [1][2][3][4][5][6][7][8][9][10][11][12][13][14] C] in the presence and absence of test plasma. The reaction was allowed to proceed with gentle shaking at 37 °C for 15 min.…”

Section: Aa Metabolism By Human Plateletsmentioning

confidence: 99%

“…The human blood plasma of adult, but not fetal, inhibits COX-1 in vitro [5,6]. Human serum also inhibits the production of prostaglandin (PG) E2, PGF 2α and PGI 2 [7] and since it inhibits COX, it was assumed that serum also inhibits the production of thromboxane (TX) A 2 .…”

Section: Introductionmentioning

confidence: 99%

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Anti-Inflammatory and Antiplatelet Activities of Plasma Are Conserved Across Twelve Mammalian Species

et al. 2014

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Human plasma inhibits arachidonic acid metabolism and platelet aggregation. This helps human form a haemostatic control system that prevents the progress of certain aggregatory or inflammatory reactions. Whether this property of plasma is unique to human or extends to other species is not well known. It is speculated that this protective ability of plasma remains evolutionarily conserved in different mammals. In order to confirm this, the effect of plasma from 12 different mammalian species was investigated for its inhibitory potential against arachidonic acid metabolism and platelet aggregation. Metabolism of arachidonic acid by cyclooxygenase and lipoxygenase pathways was studies using radio-immuno assay and thin layer chromatography while platelet aggregation in the plasma of various mammals was monitored following turbedmetric method in a dual OPEN ACCESSMolecules 2014, 19 11386 channel aggregometer. Results indicate that inhibition of AA metabolism and platelet aggregation is a common feature of plasma obtained from different mammalian species, although there exists large interspecies variation. This shows that besides human, other mammals also possess general protective mechanisms against various aggregatory and inflammatory conditions and this anti-inflammatory property of the plasma is evolutionarily conserved in mammalian species. The most likely candidates responsible for these properties of plasma include haptoglobin, albumin and lipoproteins.

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Section: Resultsmentioning

confidence: 51%

Section: Resultsmentioning

confidence: 99%

Section: Aa Metabolism By Human Plateletsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Anti-Inflammatory and Antiplatelet Activities of Plasma Are Conserved Across Twelve Mammalian Species

et al. 2014

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“…A number of plants traditionally used in inflammatory and cardiovascular diseases are known to have the ability to inhibit enzymes responsible for AA metabolism (Bukhari, 2010, Ahmad, 2011b. Apart from plants, human plasma and lipoproteins are also reported to possess significant inhibitory activities against AA metabolites and platelet aggregation and form an important endogenous protective system (Saeed, 2007b, Aslam, 2008.Our study suggests that AA metabolism inhibitory constituents as well as platelet inhibitory constituents of AS are concentrated in the butanolic fraction. Therefore, it is likely that traditionally reported antiinflammatory and cardiovascular activities of AS are mediated through inhibition of COX and LOX pathways.…”

Section: Discussionmentioning

confidence: 74%

Anti-Inflammatory and Anti-Platelet Activities of Avena Sativa are Mediated through the Inhibition of Cyclooxygenase and Lipoxygenase Enzymes

Ahmed

Gul²,

Gul³

et al. 2013

Int. j. endorsing health sci. res.

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Engineering Ecotin for Identifying Proteins with a Trypsin Fold

Sathler

Craik

Takeuchi

et al. 2009

Appl Biochem Biotechnol

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Ecotin is a bidentate, fold-specific inhibitor of mammalian serine-proteases produced by Escherichia coli. This molecule may be engineered to increase and/or change its affinity and specificity providing significant biotechnological potential. Since ecotin binds tightly to serine proteases of the trypsin fold, it may help to identify the role of these enzymes in different biological processes. In this work, we tested ecotin variants as an affinity purification reagent for identifying enzymes in samples of tumor progression and mammary gland involution. Initially, we used a commercial source of urokinase-type plasminogen activator (u-PA) that remained fully active after elution from an affinity column of the ecotin variant (M84R, M85R). We then successfully identified u-PA from more complex mixtures including lysates from a prostate cancer cell line and involuting mouse mammary glands. Interestingly, a membrane-type serine protease 1 was isolated from the Triton X-100-solubilized PC-3 cell lysates, and surprisingly, haptoglobin, a serine-protease homolog protein, was also identified in mammary gland lysates and in blood. Haptoglobin does not prevent ecotin inhibition of u-PA, but it may act as a carrier within blood when ecotin is used in vivo. Finally, this affinity purification matrix was also able to identify a thrombin-like enzyme from snake venom using an ecotin variant directed against thrombin. Overall, the ecotin variants acted as robust tools for the isolation and characterization of proteins with a trypsin fold. Thus, they may assist in the understanding of the role of these serine proteases and homologous proteins in different biological processes.

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Dual inhibition of cyclooxygenase and lipoxygenase by human haptoglobin: Its polymorphism and relation to hemoglobin binding

Cited by 49 publications

References 21 publications

Anti-Inflammatory and Antiplatelet Activities of Plasma Are Conserved Across Twelve Mammalian Species

Anti-Inflammatory and Antiplatelet Activities of Plasma Are Conserved Across Twelve Mammalian Species

Anti-Inflammatory and Anti-Platelet Activities of Avena Sativa are Mediated through the Inhibition of Cyclooxygenase and Lipoxygenase Enzymes

Engineering Ecotin for Identifying Proteins with a Trypsin Fold

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