Paraoxonase-1 Inhibits Oxidized Low-Density Lipoprotein-Induced Metabolic Alterations and Apoptosis in Endothelial Cells: A Nondirected Metabolomic Study

García-Heredia, Anabel; Marsillach, Judit; Rull, Anna; Triguero, Iris; Fort, Isabel; Mackness, Bharti; Mackness, Michael I.; Shih, Diana M.; Joven, Jorge; Camps, Jordi

doi:10.1155/2013/156053

Cited by 32 publications

(25 citation statements)

References 32 publications

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“…Garcia-Heredia et al used a metabolomics approach to study the effects of Ox-LDL on cultured human endothelial cells [94]. Ox-LDL induced perturbations of carbohydrate and phospholipid metabolism, specifically in hexose metabolism, glycolysis and the tricarboxylic acid cycle, decreased phospholipid synthesis and increased phospholipid breakdown.…”

Section: Physiological Roles Of Human Pon1mentioning

confidence: 99%

Human paraoxonase-1 (PON1): Gene structure and expression, promiscuous activities and multiple physiological roles

Mackness

2015

Gene

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262

214

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Human PON1 is a HDL-associated lipolactonase capable of preventing LDL and cell membrane oxidation and is therefore considered to be atheroprotective. PON1 contributes to the antioxidative function of HDL and reductions in HDL-PON1 activity, prevalent in a wide variety of diseases with an inflammatory component, is believed to lead to dysfunctional HDL which can promote inflammation and atherosclerosis. However, PON1 is multifunctional and may contribute to other HDL functions such as in innate immunity, preventing infection by quorum sensing gram negative bacteria by destroying acyl lactone mediators of quorum sensing, and putative new roles in cancer development and the promotion of healthy ageing. In this review we explore the physiological roles of PON1 in disease development, as well as PON1 gene and protein structure, promiscuous activities and the roles of SNPs and ethnicity in determining PON1 activity.

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Section: Physiological Roles Of Human Pon1mentioning

confidence: 99%

Human paraoxonase-1 (PON1): Gene structure and expression, promiscuous activities and multiple physiological roles

Mackness

2015

Gene

Self Cite

262

214

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“…For example, PON1 deficient mice have been shown to be more susceptible to lipoprotein oxidation, inflammation, atherosclerosis [12, 13, 27], and hepatic steatosis [28], whereas PON1 transgenic mice over-expressing human PON1 are more resistant to inflammation and atherosclerosis [14]. PON1 has been shown to prevent LDL oxidation in vitro [18, 19] and decreased levels of PON1 are associated with increased risk for cardiovascular disease in humans [7, 29–32].…”

Section: 1 Introductionmentioning

confidence: 99%

Inflammation, Infection, Cancer and All That…The Role of Paraoxonases

Devarajan

Shih

Reddy

2014

Advances in Experimental Medicine and Biology

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The paraoxonase (PON) gene family consists of three members, PON1, PON2 and PON3. All PON proteins possess antioxidant properties and lipo-lactonase activities, and are implicated in the pathogenesis of several inflammatory diseases including atherosclerosis, Alzheimer's, Parkinson's, diabetes and cancer. Despite the role of PON proteins in critical cellular functions and associated pathologies, the physiological substrates and molecular mechanisms by which PON proteins function as anti-inflammatory proteins remain largely unknown. PON1 is found exclusively extracellular and associated solely with high-density lipoprotein (HDL) particles in the circulation, and, in part, confers the anti-oxidant and anti-inflammatory properties associated with HDL. Recent studies demonstrated that the intracellular PON proteins; PON2 and PON3 (i) are associated with mitochondria and mitochondria-associated membranes, (ii) modulate mitochondria-dependent superoxide production, and (iii) prevent apoptosis. Overexpression of PON2 and PON3 genes protected (i) mitochondria from antimycin or oligomycin mediated mitochondrial dysfunction and (ii) ER stress and ER stress mediated mitochondrial dysfunction. These studies illustrate that the anti-inflammatory effects of PON2 and PON3 may, in part, be mediated by their role in mitochondrial and associated organelle function. Since oxidative stress as a result of mitochondrial dysfunction is implicated in the development of inflammatory diseases including atherosclerosis and cancer, these recent studies on PON2 and PON3 proteins may provide a mechanism for the scores of epidemiological studies that show a link between PON genes and numerous inflammatory diseases. Understanding such mechanisms will provide novel routes of intervention in the treatment of diseases associated with pro-inflammatory oxidative stress.

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“…Lipid peroxides present in oxLDL have been shown to stimulate ROS formation and impair oxygen consumption at Complexes I, II/III, and IV of the respiratory chain, resulting in mitochondrial dysfunction (78, 79). The HDL-associated protein PON1 performs an important antioxidant function by hydrolyzing cholesteryl esters and phospholipids in oxidized lipoproteins (79).…”

Section: Hdl and Apoa-i Preserve Mitochondrial Functionmentioning

confidence: 99%

High-Density Lipoprotein Regulation of Mitochondrial Function

White

Datta

Giordano

2017

Advances in Experimental Medicine and Biology

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Lipoproteins play a key role in regulating plasma and tissue levels of cholesterol. Apolipoprotein B (apoB)-containing lipoproteins, including chylomicrons, very-low density lipoprotein (VLDL) and low-density lipoprotein (LDL), serve as carriers of triglycerides and cholesterol and deliver these metabolites to peripheral tissues. In contrast, high-density lipoprotein (HDL) mediates Reverse Cholesterol Transport (RCT), a process by which excess cholesterol is removed from the periphery and taken up by hepatocytes where it is metabolized and excreted. Anti-atherogenic properties of HDL have been largely ascribed to apoA-I, the major protein component of the lipoprotein particle. The inflammatory response associated with atherosclerosis and ischemia-reperfusion (I-R) injury has been linked to the development of mitochondrial dysfunction. Under these conditions, an increase in reactive oxygen species (ROS) formation induces damage to mitochondrial structural elements, leading to a reduction in ATP synthesis and initiation of the apoptotic program. Recent studies suggest that HDL-associated apoA-I and lysosphingolipids attenuate mitochondrial injury by multiple mechanisms, including the suppression of ROS formation and induction of autophagy. Other apolipoproteins, however, present in lower abundance in HDL particles may exert opposing effects on mitochondrial function. This chapter examines the role of HDL-associated apolipoproteins and lipids in the regulation of mitochondrial function and bioenergetics.

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Paraoxonase-1 Inhibits Oxidized Low-Density Lipoprotein-Induced Metabolic Alterations and Apoptosis in Endothelial Cells: A Nondirected Metabolomic Study

Cited by 32 publications

References 32 publications

Human paraoxonase-1 (PON1): Gene structure and expression, promiscuous activities and multiple physiological roles

Human paraoxonase-1 (PON1): Gene structure and expression, promiscuous activities and multiple physiological roles

Inflammation, Infection, Cancer and All That…The Role of Paraoxonases

High-Density Lipoprotein Regulation of Mitochondrial Function

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