A possible antiatherogenic role for phosphocitrate through modulation of low density lipoprotein uptake and degradation in aortic smooth muscle cells

Ward, Leigh C.; Shankar, Ravi; Sallis, John D.

doi:10.1016/0021-9150(87)90013-x

Cited by 15 publications

(4 citation statements)

References 20 publications

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“…It should be noted that citrate and phosphocitrate bear different anionic charges at the test pH (8.50). Citrate (citric acid has pK a values of 3.13, 4.76, and 6.40 for the three -COOH groups) and possesses a 3-charge, whereas phosphocitrate (phosphocitric acid has pK a values of of <2.00 (for -P-OH), 3.67 (for β-COOH), 5.15 (for R-COOH), 7.69 (for -P-OH), and >13.00 (for R-COOH)) 28 possesses a 4-charge at pH 8.50. It is therefore not unlikely that the increased anionic charge on phosphocitrate, and by consequence, its weaker interaction with the negative struvite surface (vide supra), is linked to its reduced inhibitory activity compared to that of citrate.…”

Section: Resultsmentioning

confidence: 99%

The Effect of Citrate and Phosphocitrate On Struvite Spontaneous Precipitation

Kofina

Demadis

Koutsoukos

2007

Crystal Growth & Design

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ABSTRACT:The effect of citrate and phosphocitrate ions on the spontaneous precipitation of magnesium ammonium phosphate hexahydrate (MgNH 4 PO 4 · 6H 2 O, struvite) at pH 8.50 and 25°C was investigated at conditions of constant solution supersaturation. The supersaturated solutions were prepared in synthetic wastewater. The presence of citrate and phosphocitrate in the working solutions showed reduction of the initial rates of struvite precipitation when compared with solutions in their absence. The parabolic dependence of the rates of precipitation on the relative solution supersaturation suggested a surfacediffusion-controlled mechanism. Presence of citrate and phosphocitrate in the supersaturated solutions at concentration levels from 1 to 10 µM resulted in a drastic increase in induction times. The presence of citrate and phosphocitrate inhibited struvite precipitation up to 75-80%. The reduction of precipitation rates was related to additive concentration following an expression suggested by the kinetic Langmuir-type adsorption model. The affinity constant calculated for citrate (8.2 × 10 5 ) was considerably higher than the respective value for phosphocitrate (0.6 × 10 5 ). Finally, it should be noted that the morphology of the prismatic, elongated struvite crystals precipitated in the presence of citrate and in the presence of phosphocitrate showed differences only in size.

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Section: Resultsmentioning

confidence: 99%

The Effect of Citrate and Phosphocitrate On Struvite Spontaneous Precipitation

Kofina

Demadis

Koutsoukos

2007

Crystal Growth & Design

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“…Several studies indicate that PC has biological activities unrelated to its anticalcification activity. For example, PC reduced the degradation of low-density lipoprotein by 60% [29]. PC inhibited transforming growth factor- β 1-induced proliferation of progressive ankylosis fibroblasts [30].…”

Section: Introductionmentioning

confidence: 99%

Phosphocitrate Is Potentially a Disease-Modifying Drug for Noncrystal-Associated Osteoarthritis

Sun

Mauerhan

Franklin

et al. 2013

BioMed Research International

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Phosphocitrate (PC), a calcification inhibitor, inhibits the development of crystal-associated osteoarthritis (OA) in Hartley guinea pigs. However, the molecular mechanisms underlying its disease-modifying effect remain elusive. This study sought to test the hypothesis that PC has calcium crystal-independent biological activities which are, at least in part, responsible for its disease-modifying activity. We found that PC inhibited the proliferation of OA fibroblast-like synoviocytes in the absence of calcium crystals. Consistent with its effect on cell proliferation, PC downregulated the expression of numerous genes classified in cell proliferation. PC also downregulated the expression of many genes classified in angiogenesis and inflammatory response including prostaglandin-endoperoxide synthase 2, interleukin-1 receptor, type I, and chemokine (C-C motif) ligand 2. In contrast, PC upregulated the expression of many genes classified in musculoskeletal tissue development, including aggrecan, type I collagen, and insulin-like growth factor binding protein 5. These findings suggest that PC is not only a promising disease-modifying drug for crystal-associated OA but also for noncrystal-associated OA.

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“…All −COOH groups are protonated due to the low pH of preparation. There are three dissociated protons per two PC molecules , all coming from −PO 3 H 2 . Unexpectedly, the second proton from −PO 3 H is dissociated before that from α-COOH and is involved in a short hydrogen bond (2.453(3) Å) connecting adjacent “ribbons”.…”

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confidence: 99%