Very low density lipoproteins provide a vector for secretion of paraoxonase-1 from cells

Deakin, Sara; Moren, Xenia; James, Richard

doi:10.1016/j.atherosclerosis.2004.08.039

Cited by 65 publications

(63 citation statements)

References 24 publications

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“…The process is well established as being atheroprotective, as is the exchange of apolipoproteins C and E between HDL and VLDL or chylomicrons. Interestingly we demonstrated recently that PON1 can also be transferred between HDL and VLDL [28].…”

Section: Discussionmentioning

confidence: 92%

HDL-associated paraoxonase-1 can redistribute to cell membranes and influence sensitivity to oxidative stress

Deakin

Bioletto

Bochaton‐Piallat

et al. 2011

Free Radical Biology and Medicine

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a b s t r a c t a r t i c l e i n f oParaoxonase-1 (PON1) is a high-density lipoprotein (HDL)-associated serum enzyme thought to make a major contribution to the antioxidant capacity of the lipoprotein. In previous studies, we proposed that HDL promoted PON1 secretion by transfer of the enzyme from its plasma membrane location to HDL transiently anchored to the hepatocyte. This study examined whether PON1 can be transferred into cell membranes and retain its enzymatic activities and functions. Using Chinese hamster ovary and human endothelial cells, we found that recombinant PON1 as well as PON1 associated with purified human HDL was freely exchanged between the external medium and the cell membranes. Transferred PON1 was located in the external face of the plasma membrane of the cells in an enzymatically active form. The transfer of PON1 led to a gain of function by the target cells, as revealed by significantly reduced susceptibility to oxidative stress and significantly increased ability to neutralize the bacterial virulence agent 3-oxo-C 12 -homoserine lactone. The data demonstrate that PON1 is not a fixed component of HDL and suggest that the enzyme could also exert its protective functions outside the lipoprotein environment. The observations may be of relevance to tissues exposed to oxidative stress and/or bacterial infection.

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Section: Discussionmentioning

confidence: 92%

HDL-associated paraoxonase-1 can redistribute to cell membranes and influence sensitivity to oxidative stress

Deakin

Bioletto

Bochaton‐Piallat

et al. 2011

Free Radical Biology and Medicine

Self Cite

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“…The genotypes of the PON1 Q192R , PON1 L55M , PON1 C-108T , and PON1 A-162G polymorphisms were determined as previously published (34)(35)(36). All of the 91 CAAD and 171 of the 184 non-CAAD subjects also had genotyping performed for the PON1 55 polymorphism by Illumina, Inc. There was a 1% difference in genotypes.…”

Section: Pon1 Genotype and Activity Measuresmentioning

confidence: 99%

“…The current study evaluated the effects of PON1 activities in the hydrolysis of paraoxon, diazoxon, and phenylacetate as well as the genotype at functional, common promoter region ( PON1 Ϫ 162 and PON1 Ϫ 108 ) and coding ( PON1 55 and PON1 192 ) polymorphisms on lipids and lipoproteins in subjects with and without carotid artery disease (CAAD). The aim was to determine which PON1 parameters are most correlated with these known cardiovascular risk factors, with the eventual goal of determining whether any role of PON1 in vascular disease may be attributable, in part, to PON1's relationship with lipids, lipoproteins, and apolipoproteins.…”

mentioning

confidence: 99%

The correlation of paraoxonase (PON1) activity with lipid and lipoprotein levels differs with vascular disease status

Rozek

Hatsukami

Richter

et al. 2005

Journal of Lipid Research

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Paraoxonase (PON1) is an HDL-associated enzyme. Low PON1 activity predicts vascular disease status and is a more reliable predictor of vascular disease than are functional PON1 genotypes. There is evidence that the relationship of PON1 to vascular disease is, in part, due to its antioxidant activity. However, the physical relationship of PON1 with HDL and the existence of cholesterol pathway regulatory elements at the PON1 locus suggest a further relationship of PON1 with lipoproteins, which may contribute to its role in vascular disease. We investigated the relationship of PON1 activity and genotype to lipid-related traits in 91 Caucasian men with severe carotid artery disease and 184 without vascular disease who were not on lipid-lowering medications. Prior studies of PON1 relationship to lipids have not stratified by disease status.We found that PON1 activity was correlated with HDL traits in controls and with LDLand VLDL-related traits in cases. We hypothesize differences in the joint regulation of PON1 and lipoproteins in cases and controls. -Rozek, L. S., T.

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“…The enrichment of VLDL and enhancement of PON activity might be associated, as in a previous study (22) in which VLDL was able to promote secretion of PON-1 from Chinese hamster ovary cells and stabilize the activity. They also showed that VLDL-associated PON-1 retains its antioxidant function.…”

Section: Discussionmentioning

confidence: 58%

Elevated HDL2-paraoxonase and reduced CETP activity are associated with a dramatically lower ratio of LDL-cholesterol/total cholesterol in a hypercholesterolemic and hypertriglyceridemic patient

Lee

Park²,

Lee³

et al. 2010

Int J Mol Med

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Abstract.A female patient (64 years of age; body mass index, 26) had a markedly and relatively low low-density lipoprotein-cholesterol (LDL-C) level (97 mg/dl) despite high serum total cholesterol (TC) (331 mg/dl) and triacylglyceride levels (307 mg/dl). Since the expected LDL-C was 222 mg/dl, there was a significant difference between the calculation and measurement based on direct enzyme assay. Only 30% of serum cholesterol was associated with LDL-C in this patient. To determine the basis for the markedly low LDL-C/TC ratio, we isolated and analyzed lipoproteins from the patient as well as age-and gender-matched controls. The patient had lowered serum CETP activity and elevated paraoxonase activity with GOT and GPT values in the normal range. The very low-density lipoprotein particles from the patient were larger than those of the controls and enriched with lipid and protein, while the LDL from the patient (LDL-P) had a lower particle number and protein content than the controls. The LDL-P was more resistant to cupric ion-mediated oxidation. HDL 2 from the patient (HDL 2 -P) had highly enhanced paraoxonase activity and antioxidant ability. The patient had a 1.5-fold higher level of apolipoprotein (apo) A-I expression in HDL 2 . ApoA-I in HDL 2 and HDL 3 from the patient showed no fragmentation, while the control had fragmented bands (17 and 21 kDa) in the HDL. The HDL 2 -P also had a larger particle size and greater protein content with less lipid content. HDL 3 -associated cholesteryl ester transfer protein was reduced in the patient, although the particle size was similar to the controls. In conclusion, a patient who had a markedly lower LDL-C/TC ratio despite hyperlipidemia associated with higher paraoxonase activity, higher apoA-I level and lower CETP activity without fragmentation of apoA-I in the HDL fraction is presented. The enhanced antioxidant and anti-inflammatory activity of HDL might contribute to the low LDL-C/TC ratio in this patient. IntroductionDyslipidemia is an important risk factor for coronary heart disease (CHD), and low-density lipoprotein-cholesterol (LDL-C) is a strong biomarker to predict the risk of CHD (1). Patients with diabetes and metabolic syndrome have a strong association with atherogenic dyslipidemia, which includes high levels of triacylglycerides (TG) and elevated levels of small dense LDL (2). The most widely used method to calculate LDL-C is the Friedewald equation (3), although several methods of direct measurement are currently used. However, the estimated LDL-C using the Friedewald equation does not produce an accurate number when the plasma TG is >400 mg/dl or when plasma is not collected in the fasting state (4). Otherwise, a discrepancy in the number of measured LDL-C and the Friedewald LDL-C might indicate a modified lipoprotein metabolism. The National Cholesterol Education Program (NCEP) guidelines recommend development of direct assays to measure LDL-C (5) since LDL-C can be influenced by the dynamic interaction of apolipoprotein and several lipoprotein-associat...

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Very low density lipoproteins provide a vector for secretion of paraoxonase-1 from cells

Cited by 65 publications

References 24 publications

HDL-associated paraoxonase-1 can redistribute to cell membranes and influence sensitivity to oxidative stress

HDL-associated paraoxonase-1 can redistribute to cell membranes and influence sensitivity to oxidative stress

The correlation of paraoxonase (PON1) activity with lipid and lipoprotein levels differs with vascular disease status

Elevated HDL2-paraoxonase and reduced CETP activity are associated with a dramatically lower ratio of LDL-cholesterol/total cholesterol in a hypercholesterolemic and hypertriglyceridemic patient

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