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Showing 1521–1540 of 2058 publications.
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Davies, Michael J.Proteins are a major target for oxidants as a result of their abundance in biological systems, and their high rate constants for reaction. Kinetic data for a number of radicals and non-radical oxidants (e.g. singlet oxygen and hypochlorous acid) are consistent with proteins consuming the majority of these species generated within cells. Oxidation can occur at both the protein backbone and on the amino acid side-chains, with the ratio of attack dependent on a number of factors. With some oxidants, damage is limited and specific to certain residues, whereas other species, such as the hydroxyl radical, give rise to widespread, relatively non-specific damage. Some of the major oxidation pathways, and products formed, are reviewed. The latter include reactive species, such as peroxides, which can induce further oxidation and chain reactions (within proteins, and via damage transfer to other molecules) and stable products. Particular emphasis is given to the oxidation of methionine residues, as this species is readily oxidised by a wide range of oxidants. Some side-chain oxidation products, including methionine sulfoxide, can be employed as sensitive, specific, markers of oxidative damage. The product profile can, in some cases, provide valuable information on the species involved; selected examples of this approach are discussed. Most protein damage is non-repairable, and has deleterious consequences on protein structure and function; methionine sulfoxide formation can however be reversed in some circumstances. The major fate of oxidised proteins is catabolism by proteosomal and lysosomal pathways, but some materials appear to be poorly degraded and accumulate within cells. The accumulation of such damaged material may contribute to a range of human pathologies. 2004 Elsevier B.V. All rights reserved.
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Berry, Kim; Martinic, Gary[No abstract available]
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Nicholls, Stephen J.; Rye, Kerry Anne; Barter, Philip J.Purpose of review: The concentration of cholesterol in HDL is an inverse predictor of future cardiovascular disease, with evidence mounting that therapies that increase HDL concentration are antiatherogenic. The best known antiatherogenic function of HDL particles relates to their ability to promote the efflux of cholesterol from cells. However, they also have antioxidant, antiinflammatory and antithrombotic properties. Recent findings: The past year has seen the publication of several papers that highlight a potential major protective role of HDL in states of acute inflammation. Papers showing extremely promising results using novel inhibitors of cholesteryl ester transfer protein as HDL-raising agents have also appeared. Finally, the discovery that ATP-binding cassette transporter G1 (ABCG 1) transports cell cholesterol to large HDL particles in the extracellular space has largely reconciled apparent inconsistencies between basic research indicating that small, pre-?-migrating HDL particles are the antiatherogenic components of HDL and epidemiological research that implicates larger HDL particles as the protective fraction. Summary: The finding that ABCG1 promotes the efflux of cholesterol from cells to large HDL particles also provides powerful circumstantial evidence that cholesteryl ester transfer protein inhibition (which increases HDL size) may enhance, rather than reduce, cholesterol efflux, and thus inhibit the development of atherosclerosis. 2005 Lippincott Williams & Wilkins.
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Stender, Steen; Schuster, Herbert M.; Barter, Philip J.; Watkins, Claire; Kallend, David G.Aim: The metabolic syndrome (MS) increases the risk of coronary heart disease, yet few data are available on the effects of statin treatment in improving lipid measures in patients with the syndrome. This analysis compares the effects of statin therapy on plasma low-density lipoprotein cholesterol (LDL-C) goal achievement and lipid levels in hypercholesterolaemic patients with or without the MS. Methods: The Measuring Effective Reductions in Cholesterol Using Rosuvastatin TherapY I (MERCURY I) trial compared rosuvastatin 10 mg with atorvastatin 10 mg and 20 mg, simvastatin 20 mg and pravastatin 40 mg over 8 weeks in patients with coronary or other atherosclerotic diseases or diabetes who had fasting levels of LDL-C of ?2.99 mmol/l and triglycerides of <4.52 mmol/l. Modified National Cholesterol Education Program Adult Treatment Panel III (ATP III) criteria for the MS were met by 1342 (43%) of 3140 patients. Results: LDL-C goal achievement rates and reductions in LDL-C, total cholesterol and non-high-density lipoprotein cholesterol (HDL-C) were similar in patients with and without the MS within statin treatment groups; triglycerides were reduced more and HDL-C tended to be increased more in patients with the MS, as expected. Treatment with rosuvastatin 10 mg was more effective in allowing patients with and without the MS to reach European and ATP III LDL-C goals, compared to atorvastatin 10 mg, simvastatin 20 mg and pravastatin 40 mg (p < 0.0001 for all comparisons); consistently produced greater reductions in LDL-C, total cholesterol and non-HDL-C, compared to these treatments; and produced similar or greater reductions in triglycerides and increases in HDL-C, compared to the other treatments. Conclusions: Statin therapy is effective in allowing LDL-C goal achievement and improving the lipid profile in hypercholesterolaemic high-risk patients with the MS. Rosuvastatin 10 mg presents significant advantages in goal achievement and lipid lowering over other statins at commonly used doses in patients both with and without the MS. 2004 AstraZeneca UK Ltd.
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Barter, Philip J.High-density lipoprotein (HDL) removes excess cholesterol from macrophages in the artery wall, thereby reducing the rate of development of the atherosclerotic plaque. Other anti-atherogenic actions of HDL include preservation of endothelial function, inhibition of the recruitment of inflammatory cells to the developing plaque, antioxidant effects, and antithrombotic effects. Not surprisingly, large epidemiological cohort studies have identified low HDL-cholesterol (HDL-C) as a risk factor for coronary heart disease independently of levels of low-density lipoprotein cholesterol (LDL-C). Low HDL-C frequently occurs together with elevated triglycerides and the appearance of small, dense LDL, as a direct result of the metabolic changes associated with insulin resistance in conditions such as type 2 diabetes and the metabolic syndrome. The worldwide increase in these conditions and the associated increase in prevalence of low HDL-C have resulted in HDL being considered as a target for therapeutic intervention. Correction of low HDL-C should be an important target for therapy, especially in patients with type 2 diabetes and the metabolic syndrome.
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Barter, Philip J.; Hanefeld, Markolf G.[No abstract available]
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Barter, Philip J.; OBrien, Richard C.; Watts, Gerald F.; Zhu, Junren; Hu, Dayi; Ho, Cheng Chun; Tomlinson, Brian W.Y.; Cheung, Bernard Man Yung; Adam, John M.F.; Tjokroprawiro, Askandar; Waspadji, Sarwono; Cho, Hongkeun; Han, Kihoon; Kim, Sungrae; Lin, Khoo Kah; Chan, Siewpheng Pheng; Basit, Abdul; Pizzaro-Borromeo, Annette B.; Paz-Pacheco, Elizabeth T.; Sy, Rody G.; Lee, Kok Onn; Low, Lipping; Khue, Nguyen Thy; Binh, Ta VanCardiovascular disease is a leading cause of morbidity and mortality in Asia, and the burden of disease is expected to rise further in the 21st century. As in Western populations, dyslipidaemia is an important cardiovascular risk factor in Asian people. International guidelines focus on reduction of low-density lipoprotein cholesterol (LDL-C) for prevention and treatment of coronary heart disease (CHD). However, increasing body mass index and prevalence of type 2 diabetes and metabolic syndrome in Asia have highlighted the importance of low levels of high-density lipoprotein cholesterol (HDL-C) as a coronary risk factor. Therapeutic lifestyle changes and pharmacological intervention aimed at raising HDL-C, should benefit such patients. Weight loss and physical exercise are important interventions for raising HDL-C. However, to achieve target HDL-C levels pharmacological intervention is usually necessary. Current treatment options include statins, fibrates and nicotinic acid, either as monotherapy or in combination. Statins are generally regarded as the foundation of lipid-modifying therapy. Mainly via reduction of LDL-C. Both fibrates and nicotinic acid are effective in raising HDL-C levels, and reducing triglyceride-rich lipoproteins. The efficacy and safety profile of nicotinic acid demonstrated in Western populations indicates the clinical benefits of this therapy either alone or in combination with a statin. Based on the available evidence, the Pan-Asian Consensus Panel recommends that HDL-C levels should be raised to at least 1.0 mmol/L (40 mg/dL) in Asian patients with CHD or with a high level of risk for premature vascular disease, including patients at high risk with type 2 diabetes or the metabolic syndrome.
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Wu, Ted; McGrath, Kristine C.Y.; Heather, Alison KayCardiovascular disease is a major complication of diabetes mellitus, especially for patients with diabetic nephropathy. The underlying factor or pathogenic mechanism that links diabetic nephropathy with cardiovascular disease is not known. The endothelial cell adhesion molecules, intercellular adhesion molecule-1 or vascular cell adhesion molecule-1, play a crucial role in the initiation of atherosclerosis. Levels of both cell adhesion molecules are raised by the diabetic and kidney disease states. This review focuses on these important cell adhesion molecules and their role in the pathogenesis of cardiovascular disease in diabetes and diabetic nephropathy.
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Barter, Philip J.The concentration of cholesterol in high density lipoproteins (HDLs) has long been known to correlate inversely with the risk of developing premature coronary heart disease.1-8 In animal studies this relationship has been shown to be one of cause and effect. Increasing the concentration of HDLs in several animal models leads to an inhibition of atherosclerosis.9-11 The mechanism by which HDLs protect is still uncertain, although several of the known functions of these lipoproteins have anti-atherogenic potential. These functions include the ability of HDL particles to act as extracellular acceptors of cholesterol in the first step of the reverse cholesterol transport (RCT) pathway as well as anti-oxidant, antiinflammatory and anti-thrombotic properties of these lipoproteins. The best-documented function relates to the role of HDLs in RCT. 2006 Taylor & Francis, an imprint of the Taylor & Francis Group.
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Wyszynski, Diego F.; Waterworth, Dawn M.; Barter, Philip J.; Cohen, Jonathan C.; Kesaniemi, YrjAntero; Mahley, Robert W.; McPherson, Ruth M.; Waeber, Gard; Bersot, Thomas P.; Sharma, Sanjay S.; Nolan, Vikki G.; Middleton, Lefkos T.; Sundseth, Scott S.; Farrer, Lindsay A.; Mooser, Vincent E.; Grundy, Scott M.Genetic Epidemiology of Metabolic Syndrome is a multinational, family-based study to explore the genetic basis of the metabolic syndrome. Atherogenic dyslipidemia (defined as low plasma high-density lipoprotein cholesterol with elevated triglycerides (<25th and >75th percentile for age, gender, and country, respectively) identified affected subjects for the metabolic syndrome. This report examines the frequency at which atherogenic dyslipidemia predicts the metabolic syndrome of the National Cholesterol Education Program Adult Treatment Panel III (ATP-III). One thousand four hundred thirty-six (854 men/582 women) affected patients by our criteria were compared with 1,672 (737 men/935 women) unaffected persons. Affected patients had more hypertension, obesity, and hyperglycemia, and they met a higher number of ATP-III criteria (3.2 1.1 SD vs 1.3 1.1 SD, p <0.001). Overall, 76% of affected persons also qualified for the ATP-III definition (Cohen's ? 0.61, 95% confidence interval 0.59 to 0.64), similar to a separate group of 464 sporadic, unrelated cases (75%). Concordance increased from 41% to 82% and 88% for ages ?35, 36 to 55, and <55 years, respectively. Affected status was also independently associated with waist circumference (p <0.001) and fasting glucose (p <0.001) but not systolic blood pressure (p = 0.43). Thus, the lipid-based criteria used to define affection status in this study substantially parallels the ATP-III definition of metabolic syndrome in subjects aged >35 years. In subjects aged <35 years, atherogenic dyslipidemia frequently occurs in the absence of other metabolic syndrome risk factors. 2005 by Excerpta Medica Inc.
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Hung, Joseph C.; McQuillan, Brendan M.; Chapman, Caroline L.; Thompson, Peter Lindsay; Beilby, John P.Objective - Activated innate immunity is thought to be involved in the pathogenesis of metabolic syndrome and type 2 diabetes. Interleukin-18 (IL-18) is a pleiotropic proinflammatory cytokine with important regulatory functions in the innate immune response. We sought to determine whether an elevated IL-18 concentration was a risk predictor for metabolic syndrome in a community population independent of obesity and hyperinsulinemia. Methods and Results - A representative general population, aged 27 to 77 years, without clinical diabetes was studied for clinical and biochemical risk factors for metabolic syndrome. Serum IL-18 concentration measured in 955 subjects correlated with metabolic syndrome traits including body mass index (BMI), waist circumference, triglyceride, high-density lipoprotein (inversely), and fasting glucose and insulin levels (all P<0.001). Mean IL-18 levels rose progressively with the increasing number of metabolic risk factors (ANOVA P<0.001). After adjusting for age, gender, BMI, and insulin levels, increasing IL-18 tertiles were associated with an odds ratio for metabolic syndrome of 1.0, 1.42, and 2.28, respectively (P trend=0.007). The graded risk relation was even stronger in nonobese subjects and not attenuated when adjusted for C-reactive protein and IL-6 levels. Conclusion - Our findings support the hypothesis that activation of IL-18 is involved in the pathogenesis of the metabolic syndrome. 2005 American Heart Association, Inc.
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Brown, Bronwyn E.; Dean, Roger T.; Davies, Michael J.Aims/hypothesis: Previous studies have implicated the glycoxidative modification of low-density lipoprotein (LDL) by glucose and aldehydes (apparently comprising both glycation and oxidation), as a causative factor in the elevated levels of atherosclerosis observed in diabetic patients. Such LDL modification can result in unregulated cellular accumulation of lipids. In previous studies we have characterized the formation of glycated, but nonoxidized, LDL by glucose and aldehydes; in this study we examine whether glycation of LDL, in the absence of oxidation, gives rise to lipid accumulation in arterial wall cell types. Methods: Glycated LDLs were incubated with macrophage, smooth muscle, or endothelial cells. Lipid loading was assessed by HPLC analysis of cholesterol and individual esters. Oxidation was assessed by cholesterol ester loss and 7-ketocholesterol formation. Cell viability was assessed by lactate dehydrogenase release and cell protein levels. Results: Glycation of LDL by glycolaldehyde and methylglyoxal, but not glucose (in either the presence or absence of copper ions), resulted in cholesterol and cholesterol ester accumulation in macrophage cells, but not smooth muscle or endothelial cells. The extent of lipid accumulation depends on the degree of glycation, with increasing aldehyde concentration or incubation time, giving rise to greater extents of particle modification and lipid accumulation. Modification of lysine residues appears to be a key determinant of cellular uptake. Conclusions/interpretation: These results are consistent with LDL glycation, in the absence of oxidation, being sufficient for rapid lipid accumulation by macrophage cells. Aldehyde-mediated "carbonyl-stress" may therefore facilitate the formation of lipid-laden (foam) cells in the artery wall. Springer-Verlag 2005.
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Orange, Stefan J.; Rasko, John E.J.; Thompson, John F.; Vaughan, Janet I.; Olive, Emily C.; Pedler, Michelle; Horvath, John Stephen; Hennessy, AnnemarieIn pregnancy, the placental contribution of cytokines to maternal immunosuppression has been established, however their role in normal maternal blood pressure regulation has not been identified. We investigate the contribution of interleukin-10 (IL-10) and tumor necrosis factor-? (TNF-?) to the vasodilation of early pregnancy in non-human primates. We also sequenced the IL-10 baboon gene and compared it with humans. The effect of four different treatments, administered sequentially (semi-random-design) on resting 18 h, night time, or hourly mean arterial pressure (MAP) and heart rate (HR) were measured using telemetry. An anti-human IL-10 monoclonal antibody (MAb, 1 mg, n = 7), anti-TNF-? antibody (n = 3), a combination of anti-IL-10 and anti-TNF-? antibodies (n = 5) or saline (n = 3) control were administered intravenously to baboons in early pregnancy. Plasma and placental IL-10 concentration was measured before and after injection in all animals. Anti-human IL-10 MAb caused a significant increase in MAP of 2.6 0.5 mmHg over the 18-h period (p < 0.05). Administration of TNF-? alone or in combination with IL-10 did not alter MAP. There was 97% sequence homology of IL-10 cDNA between humans and baboons. IL-10 was shown to regulate the vasodilation of early pregnancy in Papio hamadryas. This partial role of IL-10 in the early BP response of primate pregnancy may be relevant to pathophysiological states of human pregnancy such as preeclampsia. 2004 Elsevier Ltd. All rights reserved.
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Barter, Philip J.[No abstract available]
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Nicholls, Stephen J.; Dusting, Gregory James; Di Bartolo, Belinda Ann; Bao, Shishan San; Drummond, Grant R.; Rye, Kerry Anne; Barter, Philip J.Background - HDLs have antiinflammatory and antioxidant properties in vitro. This study investigates these properties in vivo. Methods and Results - Chow-fed, normocholesterolemic New Zealand White rabbits received a daily infusion of (1) saline, (2) reconstituted HDL (rHDL) containing 25 mg apolipoprotein (apo) A-I and 50 mg of either 1-palmitoyl-2-linoleoyl phosphatidylcholine (PLPC) or 1,2-dipalmitoyl phosphatidylcholine (DPPC), (3) 25 mg lipid-free apoA-I, or (4) 50 mg of either PLPC-small unilamellar vesicles (SUVs) or DPPC-SUVs on each of 3 consecutive days. Nonocclusive carotid periarterial collars were implanted after the second dose of treatment. Forty-eight hours after insertion of the collars, the arteries were removed and analyzed for the presence of reactive oxygen species, the infiltration of neutrophils, and the expression of adhesion proteins and chemokines. Insertion of the periarterial collar induced a 4.1-fold increase in presence of vascular wall reactive oxygen species. This effect was completely abolished in the animals infused with rHDL. The periarterial collar was associated with a dense infiltration of the arterial wall by polymorphonuclear leukocytes. This infiltration was inhibited by 73% to 94% in the animals infused with rHDL, by 75% in the animals infused with lipid-free apoA-I, and by 51% to 65% in animals infused with SUVs. There were no significant differences between the effects of PLPC and DPPC in either the rHDL or SUVs. Endothelial expression of vascular cell adhesion molecule-1, intercellular adhesion molecule-1, and monocyte chemoattractant protein-1 was also increased by the collar insertion and inhibited by rHDL, lipid-free apoA-I, and, to a lesser extent, also by the SUVs. Conclusions - Infusion of rHDL, apoA-I, and phospholipid-SUVs inhibits the early pro-oxidant and proinflammatory changes induced by a periarterial collar in normocholesterolemic rabbits. 2005 American Heart Association, Inc.
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Morgan, Philip E.; Treweek, Teresa M.; Lindner, Robyn A.; Price, William E.; Carver, John A.Under conditions of stress, such as elevated temperature, molecular chaperones stabilize proteins from unfolding, aggregating, and precipitating. We have investigated the chaperone activity of the major milk proteins ?<inf>s</inf>-, ?-, and ?-casein with reduced insulin and the milk whey proteins, ?-lactalbumin and ?-lactoglobulin, and compared it with that of the mammalian small heat shock protein (sHsp), ?-crystallin, and clusterin. ?<inf>s</inf>-Casein exhibited different chaperone behavior under reduction and heat stresses, i.e., chaperone activity increased with increasing temperature (as observed with ?-crystallin), but under reduction stress, its chaperone activity increased at lower temperatures, ?- and ?-casein had comparable chaperone ability with each other but were less effective than ?<inf>s</inf>-casein. Under molecular crowding conditions, precipitation of stressed protein was accelerated, and ?<inf>s</inf>-casein was a poorer chaperone. Furthermore, at slightly alkaline pH values, ?<inf>s</inf>- casein was a less effective chaperone than at neutral pH. Detailed fluorescence, size exclusion chromatography, and real-time NMR studies studies indicated that the casein proteins underwent conformational changes and stabilized the partially unfolded whey proteins prior to formation of high molecular weight soluble complexes. These results are consistent with casein proteins acting as molecular chaperones in a manner similar to sHsps and clusterin. 2005 American Chemical Society.
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LaRosa, John C.; Grundy, Scott M.; Waters, David D.; Shear, Charles L.; Barter, Philip J.; Fruchart, Jean Charles; Gotto, Antonio M.; Greten, Heiner; Kastelein, Johannes Jacob Pieter; Shepherd, James; Wenger, Nanette KassBACKGROUND: Previous trials have demonstrated that lowering low-density lipoprotein (LDL) cholesterol levels below currently recommended levels is beneficial in patients with acute coronary syndromes. We prospectively assessed the efficacy and safety of lowering LDL cholesterol levels below 100 mg per deciliter (2.6 mmol per liter) in patients with stable coronary heart disease (CHD). METHODS: A total of 10,001 patients with clinically evident CHD and LDL cholesterol levels of less than 130 mg per deciliter (3.4 mmol per liter) were randomly assigned to double-blind therapy and received either 10 mg or 80 mg of atorvastatin per day. Patients were followed for a median of 4.9 years. The primary end point was the occurrence of a first major cardiovascular event, defined as death from CHD, nonfatal non-procedure-related myocardial infarction, resuscitation after cardiac arrest, or fatal or nonfatal stroke. RESULTS: The mean LDL cholesterol levels were 77 mg per deciliter (2.0 mmol per liter) during treatment with 80 mg of atorvastatin and 101 mg per deciliter (2.6 mmol per liter) during treatment with 10 mg of atorvastatin. The incidence of persistent elevations in liver aminotransferase levels was 0.2 percent in the group given 10 mg of atorvastatin and 1.2 percent in the group given 80 mg of atorvastatin (P<0.001). A primary event occurred in 434 patients (8.7 percent) receiving 80 mg of atorvastatin, as compared with 548 patients (10.9 percent) receiving 10 mg of atorvastatin, representing an absolute reduction in the rate of major cardiovascular events of 2.2 percent and a 22 percent relative reduction in risk (hazard ratio, 0.78; 95 percent confidence interval, 0.69 to 0.89; P<0.001). There was no difference between the two treatment groups in overall mortality. CONCLUSIONS: Intensive lipid-lowering therapy with 80 mg of atorvastatin per day in patients with stable CHD provides significant clinical benefit beyond that afforded by treatment with 10 mg of atorvastatin per day. This occurred with a greater incidence of elevated aminotransferase levels. Copyright 2005 Massachusetts Medical Society.
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Pattison, David I.; Davies, Michael J.Hypochlorous acid (HOCl) is a powerful oxidant generated from H <inf>2</inf>O<inf>2</inf> and chloride ions by the heme enzyme myeloperoxidase (MPO) released from activated leukocytes. In addition to its potent antibacterial effects, excessive HOCl production can lead to host tissue damage, with this implicated in human diseases such as atherosclerosis, cystic fibrosis, and arthritis. HOCl reacts rapidly with biological materials, with proteins being major targets. Chlorinated amines (chloramines) formed from Lys and His side chains and ?-amino groups on proteins are major products of these reactions; these materials are however also oxidants and can undergo further reactions. In this study, the kinetics of reaction of His side-chain chloramines with other protein components have been investigated by UV/visible spectroscopy and stopped flow methods at pH 7.4 and 22C, using the chloramines of the model compound 4-imidazoleacetic acid and N-?-acetyl-histidine. The second-order rate constants decrease in a similar order (Cys > Met > disulfide bonds > Trp ? ?-amino > Lys ? Tyr > backbone amides > Arg) to the corresponding reactions of HOCl, but are typically 5-25 times slower. These rate constants are consistent with His side-chain chloramines being important secondary oxidants in HOCl-mediated damage. These studies suggest that formation and subsequent reactions of His side-chain chloramines may be responsible for the targeted secondary modification of selected protein residues by HOCl that has previously been observed experimentally and highlight the importance of chloramine structure on their subsequent reactivity. 2005 American Chemical Society.
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Raftery, Mark J.; Campbell, Ross; Glaros, Elias N.; Rye, Kerry Anne; Halliday, Glenda Margaret; Jessup, Wendy K.; Garner, BrettApolipoprotein-E (apoE) plays an important role in neuronal lipid transport and is thought to stabilize microtubules by preventing tau hyperphosphorylation. ApoE is also associated with insoluble amyloid detected in Alzheimer disease brain lesions. The apoE C-terminal shares several physicochemical features with ?-synuclein, another neuronal apolipoprotein-like protein. ?-Synuclein is phosphorylated by protein kinase CK2 (CK2) at an atypical PSD/E motif in vivo and in vitro. We identified a similar PSD/E motif in apoE and therefore investigated its potential phosphorylation by CK2 in vitro. When a [32P]-labeling approach was used, CK2 readily phosphorylated purified human apoE as well as recombinant forms of human apoES and apoE4. Using liquid chromatography mass spectrometry techniques, we mapped the major apoE CK2 phosphorylation site to Ser296 within the apoE PSD/E motif. We also found that apoE potently activated CK2 as demonstrated by increased CK2? subunit autophosphorylation and by increased phosphorylation of tau when the latter was added to the kinase reaction mixtures. Other proteins such as apolipoprotein A-I and albumin did not effectively activate CK2. The phosphorylation of apoE by CK2 as well as the activation of CK2 by apoE may be relevant in vivo where apoE, CK2, and tau are co-localized with additional CK2 targets on neuronal microtubules. 2005 American Chemical Society.
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Jis, Minna T.; Metso, Jari; Lankinen, Hilkka M.; Strandin, Tomas M.; Olkkonen, Vesa M.; Rye, Kerry Anne; Jauhiainen, Matti Sakari; Ehnholm, Christian P.Phospholipid transfer protein (PLTP) exists in a high-activity (HA-PLTP) and a low-activity form (LA-PLTP) in the circulation. LA-PLTP is associated with apoA-I while the HA-PLTP complex is enriched with apoE. To study the interaction of PLTP with apolipoproteins, we carried out surface plasmon resonance analyses. These demonstrated a concentration-dependent binding of recombinant human PLTP, which represents an active PLTP form, and LA-PLTP to apoE, apoA-I, and apoA-IV within a nanomolar K<inf>D</inf> range. To study whether LA-PLTP can be transformed into an active form, we incubated it in the presence of proteoliposomes containing apoE, apoA-I or apoA-IV. The apoE proteoliposomes induced a concentration-dependent activation of LA-PLTP. ApoA-IV proteoliposomes also activated LA-PLTP in a concentration-dependent manner, whereas apoA-I proteoliposomes had no such effect. These observations suggest that PLTP is capable of interacting with apoE, apoA-I, and apoA-IV, and that these interactions regulate PLTP-activity levels in plasma. 2005 Elsevier Inc. All rights reserved.
