4-hydroxynonenal, a metabolite of lipid peroxidation, activates phospholipase D in vascular endothelial cells

Natarajan, Viswanathan; Scribner, William M.; Taher, Mohiuddin M.

doi:10.1016/0891-5849(93)90036-t

Cited by 68 publications

(25 citation statements)

References 34 publications

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“…2). In general, urinary TBARS levels were considerably higher than urinary MDA concentrations determined by HPLC, and were correlated with them in a linear fashion r = 0.88 for day 1 measurements, r = 0.76 for days [5][6][7][8][9][10]. This suggests that measurement of urinary TBARS spectrophotometrically assesses a mixture of MDA and non-MDA adducts, including some that increase after oxidative stress or lipid peroxidation.…”

Section: Tbars and Mda Levelsmentioning

confidence: 85%

“…Most importantly, they react with the polyunsaturated fatty acid side chains of membrane lipids. This initiates lipid peroxidation, resulting in the generation of ethane, pentane, 4-hydroxynonenal, and malondialdehyde (MDA) [4][5][6]. Therefore, levels of lipid peroxidation products excreted in urine may serve as markers of ROImediated injury.…”

Section: Introductionmentioning

confidence: 99%

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Association of Lipid Peroxidation with Antenatal Betamethasone and Oxygen Radical Disorders in Preterm Infants

Weinberger

Anwar²,

Henien³

et al. 2004

Neonatology

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Introduction: Premature infants are highly susceptible to ‘oxygen radical diseases’ (ORD), including bronchopulmonary dysplasia, intraventricular hemorrhage/white matter injury, retinopathy of prematurity, and necrotizing enterocolitis. The incidence of ORD is reduced following antenatal treatment with betamethasone. Oxidant-mediated injury is characterized at the cellular level by peroxidation of lipid membranes. This results in the generation of malondialdehyde (MDA), which can be quantified indirectly by measurement of thiobarbituric acid-reacting substances (TBARS). There is currently no effective way to quantify the risk for ORD. In this study, we analyzed the correlation of early urinary MDA and TBARS with prenatal betamethasone administration and with the development of ORD. Methods: Preterm infants (<30 weeks gestation, n = 25) born at St. Peter’s University Hospital were enrolled. Urine samples were collected during the first 10 days of life and stored at –70°C for 0–21 days. TBARS were quantified by spectrophotometric assay, and malondialdehyde levels measured by HPLC. Subjects were screened for the subsequent development of ORD. Betamethasone administration was defined as one or more doses ≧24 h prior to delivery. Results: Urinary MDA levels increased on days 2–3 and 5–10 relative to day 1 from birth. Maximal urinary MDA concentrations were significantly higher in the ORD group compared to controls, and there was a trend toward increased urinary TBARS in the presence of ORD. Infants receiving prenatal betamethasone demonstrated higher maximal urinary TBARS values during the first 10 days of life than control infants. The length of sample storage from 0 to 3 weeks at –70°C did not significantly affect TBARS measurements. Conclusions: Elevated urinary MDA measurements in the first 10 days are correlated with the risk for ORD. Urinary TBARS concentrations, which are correlated with MDA measurements, can be quantified rapidly and are stable for short-term storage. Our findings suggest that urinary TBARS may be adaptable as a practical tool for assessing the risk for ORD in neonatal intensive care unit patients, allowing clinicians to optimize the use of preventive strategies. Antenatal betamethasone is associated with increased urinary TBARS in the first 10 days of life, indicating that the protective effects of corticosteroids are not mediated through reductions in oxidant-mediated lipid peroxidation.

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Section: Tbars and Mda Levelsmentioning

confidence: 85%

Section: Introductionmentioning

confidence: 99%

Association of Lipid Peroxidation with Antenatal Betamethasone and Oxygen Radical Disorders in Preterm Infants

Weinberger

Anwar²,

Henien³

et al. 2004

Neonatology

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“…Although the current study has not characterized any of the Michael adducts formed in lung microvascular ECs, it has been demonstrated that HNE-protein adduct accumulation reflects cellular toxicity compromising tissue survival during heart ischemia, ischemia/reperfusion injury, or pulmonary diseases (18, 19, 38 -40). Exogenously added or endogenously generated in cells, 4-HNE modulates protein function; examples include Na-K-ATPase (57), glucose transporter (58), MAPKs (7)(8)(9)(10)(11)24), phospholipases (1,4,5,59,60), protein kinase C (6), IK␤ kinase (61), and gene expression of ␥-glutamylcysteine synthetase (62). Thus, 4-HNE generated during lipid peroxidation can serve as an extracellular and intracellular signaling molecule altering cellular responses to stress and toxicity.…”

Section: Fig 11 4-hne Induces Actin Fiber Rearrangement In Ecsmentioning

confidence: 99%

Role of Mitogen-activated Protein Kinases in 4-Hydroxy-2-nonenal-induced Actin Remodeling and Barrier Function in Endothelial Cells

Usatyuk

Natarajan

2004

Journal of Biological Chemistry

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150

106

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“…7 ␤ -hydroperoxycholestenol is the primary cytotoxin of oxidized LDL (30) and 4-hydroxynonenal activates EC phospholipase D (31). Of the known lipid components of oxidized LDL, lysophosphatidylcholine (lysoPC) is perhaps the most pluripotent (see Discussion).…”

Section: Introductionmentioning

confidence: 99%

Role of lysophosphatidylcholine in the inhibition of endothelial cell motility by oxidized low density lipoprotein.

Murugesan¹,

Fox²

1996

J. Clin. Invest.

104

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Endothelial cell (EC) movement is required for the development and repair of blood vessels. We have previously shown that LDL oxidized by transition metals almost completely suppressed the wound-healing migratory response of vascular EC in vitro. We now report that lysophosphatidylcholine (lysoPC), a lipid component of oxidized LDL, has an important role in the antimigratory activity of the lipoprotein. Purified 1-palmitoyl lysoPC inhibited movement with a halfmaximal activity at 12-15 M, and near complete inhibition at 20 M; the inhibitory concentration of lysoPC was consistent with its abundance in oxidized LDL. The inhibition was not due to cytotoxicity since protein synthesis was unaffected and since EC movement was restored after removal of lysoPC. Lysophospholipid activity was dependent on lipid structure. LysoPC's containing 1-position C 16 or C 18 saturated fatty acids were antimigratory, but those containing C Յ 14 saturated fatty acids or polyunsaturated fatty acids were not. The activity of 1-palmitoyl lysolipids with various head groups was examined. Lysophosphatidylinositol was more antimigratory than lysophosphatidylglycerol and lysophosphatidylcholine, which were more potent than lysophosphatidylserine and lysophosphatidylethanolamine. Monoglyceride was inactive while lysophosphatidate had promigratory activity. These results are consistent with head group size rather than charge as a critical determinant of activity. To show that lysophospholipids within an intact lipoprotein were active, LDL was treated with bee venom phospholipase A 2 (PLA 2 ). The modified lipoprotein inhibited EC movement to the same extent as iron-oxidized LDL and antimigratory activity correlated with the amount of lysoPC formed. To determine antimigratory activity of lysoPC present in oxidized LDL, lipid extracts from oxidized LDL were fractionated by normal phase HPLC. The fraction comigrating with lysoPC had nearly the same activity as the total extract confirming that lysoPC (or a co-eluting lipid) was a major antimigratory molecule in oxidized LDL. These studies demonstrate that lysoPC

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4-hydroxynonenal, a metabolite of lipid peroxidation, activates phospholipase D in vascular endothelial cells

Cited by 68 publications

References 34 publications

Association of Lipid Peroxidation with Antenatal Betamethasone and Oxygen Radical Disorders in Preterm Infants

Association of Lipid Peroxidation with Antenatal Betamethasone and Oxygen Radical Disorders in Preterm Infants

Role of Mitogen-activated Protein Kinases in 4-Hydroxy-2-nonenal-induced Actin Remodeling and Barrier Function in Endothelial Cells

Role of lysophosphatidylcholine in the inhibition of endothelial cell motility by oxidized low density lipoprotein.

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