ORCID Profile
0000-0002-8509-3490
Current Organisation
Peter Doherty Institute
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Publisher: Xia & He Publishing
Date: 12-06-2023
Publisher: Informa UK Limited
Date: 07-1995
Publisher: Elsevier BV
Date: 11-1995
Publisher: Informa UK Limited
Date: 1991
DOI: 10.3109/02713689109001738
Abstract: Sonication of bovine alpha-crystallin increases its molecular mass from around 770 kDa to in excess of 2,300 kDa. Exposure to 2M urea or 0.1 M glycine pH 7, did not affect the size of the sonicated protein, indicating that it did not consist of dimers and higher polymers of the original molecule. Sonication of a mixture of alpha-crystallins labelled on the A chain sulphydryl group with either an aminonaphthalene or a fluorescein chromophore, generated a product exhibiting substantial energy transfer. The average distance between the probes was calculated to be 5 nm. These observations suggest that sonication has generated a new quaternary structure, incorporating subunits from two or more different alpha-crystallin molecules. No significant differences were observed in the microenvironments of tryptophan residues although those in the sonicated protein could be more easily exposed by controlled denaturation with urea. A small decrease was observed in the quenchability of a fluorescent probe attached to the sulphydryl group and a small increase in the uptake of an hydrophobic probe. These data suggest that sonication may have altered the conformation of the subunits at, or near the surface of the protein.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 14-12-2004
DOI: 10.1161/01.CIR.0000149748.79945.52
Abstract: Background— Impaired endothelium-dependent NO-mediated vasodilation is a key feature of essential hypertension and may precede the increase in blood pressure. We investigated whether transport of the NO precursor l -arginine is related to decreased endothelial function. Methods and Results— Radiotracer kinetics ([ 3 H] l -arginine) were used to measure forearm and peripheral blood mononuclear cell arginine uptake in hypertensive subjects (n=12) and in 2 groups of healthy volunteers with (n=15) and without (n=15) a family history of hypertension. In conjunction, forearm blood flow responses to acetylcholine and sodium nitroprusside were measured before and after a supplemental intra-arterial infusion of l -arginine. In vivo and in vitro measures of l -arginine transport were substantially reduced in the essential hypertension and positive family history groups compared with the negative family history group however, no difference was detected in peripheral blood mononuclear cell mRNA or protein expression levels for the cationic amino acid transporter CAT-1. Plasma concentrations of l -arginine and N G , N G′ -dimethylarginine (ADMA) did not differ between groups. l -Arginine supplementation improved the response to acetylcholine only in subjects with essential hypertension and positive family history. Conclusions— Similar to their hypertensive counterparts, normotensive in iduals at high risk for the development of hypertension are characterized by impaired l -arginine transport, which may represent the link between a defective l -arginine/NO pathway and the onset of essential hypertension. The observed transport defect is not due to apparent alterations in CAT-1 expression or elevated endogenous ADMA.
Publisher: Elsevier BV
Date: 12-2009
DOI: 10.1016/J.BIOCEL.2009.08.008
Abstract: Under conditions of oxidative stress it is well known that the bioavailability of nitric oxide (NO) is known to be significantly reduced. This process is in part due to the combination of NO with superoxide radicals to form peroxynitrite (ONOO(-)). While this process inactivates NO per se, it is not certain to which extent this process may also further impair ongoing NO production. Given the pivotal role of arginine availability for NO synthesis we determined the impact of ONOO(-) on endothelial arginine transport and intracellular arginine metabolism. Peroxynitrite reduced endothelial [(3)H]-L-arginine transport and increased the rate of arginine efflux in a concentration-dependent manner (both p<0.05). In conjunction, exposure to ONOO(-) significantly reduced the intracellular concentration of L-arginine, N(G)-hydroxy-L-arginine (an intermediate of NO biosynthesis) and citrulline by 46%, 45% and 60% respectively (all p<0.05), while asymmetric dimethyl arginine (ADMA) levels rose by 180% (p<0.05). ONOO(-) exposure did not alter the cellular distribution of the principal L-arginine transporter, CAT1, rather the effect on CAT1 activity appeared to be mediated by protein nitrosation. Conclusion Peroxynitrite negatively influences NO production by combined effects on arginine uptake and efflux, most likely due to a nitrosative action of ONOO(-) on CAT-1.
Publisher: Elsevier BV
Date: 2008
DOI: 10.1016/J.BIOCEL.2007.10.027
Abstract: The action of oxidatively modified low-density lipoprotein on vascular endothelial cells has been proposed to be a crucial process leading to endothelial dysfunction and atherogenesis. However, the biochemical mechanism for such action is not clear. We have previously shown that arginine uptake and metabolism are major determinants of endothelial function in heart failure and hypertension. In the present study we therefore aimed to assess the effects of oxidized LDL, a major pro-atherogenic molecule, on endothelial l-arginine metabolism and its uptake. Endothelial cells were exposed to oxidized LDL or native LDL for 24h, and the resultant effects on (1) the intracellular content of arginine and its major metabolites including citrulline, N(G)-hydroxy-l-arginine, asymmetric dimethylarginine, symmetric dimethylarginine and ornithine, (2) [3H]-l-arginine uptake and, (3) the pattern of distribution of cationic amino acid transporter 1, the principal l-arginine transporter, by confocal microscopy. Oxidized LDL (100 microg/mL) reduced intracellular arginine and N(G)-hydroxy-l-arginine contents by 56 and 71% (P<0.05), respectively, with a concomitant 205% increase in ADMA (P<0.05). In conjunction, oxidized LDL reduced endothelial uptake of [3H]-arginine by 60%. Furthermore, incubation of endothelial cells with oxLDL led to internalization of cationic amino acid transporter 1. We demonstrate a novel mechanism, reduced l-arginine transport, by which oxidized LDL impairs the ability of the endothelium to generate nitric oxide.
Publisher: MDPI AG
Date: 28-01-2023
DOI: 10.20944/PREPRINTS202301.0515.V1
Abstract: Cells produce reactive oxygen species (ROS) as by-products of metabolism, which can give rise to a two-sided effect on the body under balanced and imbalanced oxidant homeostasis conditions. Antioxidant supplements exert their beneficial efficacy in the treatment of metabolic diseases only when the oxidant homeostasis is imbalanced with the over-production of ROS. Over-supplementation of antioxidant(s) can also cause an imbalanced oxidant homeostasis to exert detriments to the induction of metabolic diseases. This commentary raises a concern that prior to precise supplementation of antioxidants, an establishment of oxidant homeostasis status is required in avoiding an imbalanced oxidant homeostasis in vivo. In searching for valid oxidant stress makers, 3-Nitrotyrosine seems to fit in with the selection criteria and its quantification can be correlated with the degree of oxidative stress in vivo.
Publisher: Elsevier BV
Date: 07-1994
Abstract: The distribution of glutathione reductase activity in concentric layers from the lens has been determined as a function of age for 16 species. Primate lenses have almost ten times the level of glutathione reductase found in other species. Comparison with the activity of hexokinase revealed that this is not due to a higher overall rate of metabolism in these lenses. By contrast, the higher activity found in bird and fish lenses reflects a higher metabolic activity in these tissues. In all species, a gradient of activity was observed with the highest specific activity in the outermost cortical fibres, decreasing to virtually no activity in the inner parts of the tissue. No alterations were found in this gradient with increasing age, other than an increase in the amount of nuclear tissue essentially devoid of activity. The maximum activity in the outer cortical fibres was the same, regardless of the age of the lens. The time taken, in different species, for the specific activity to decrease by half, was estimated from the rate of protein accumulation. This time was found to vary from a few days to several years, indicating that the decrease in activity is not due to ageing but rather, it is related to the maturation of fibre cells. These observations are discussed in terms of current concepts of lens ageing and cataract formation.
Publisher: Informa UK Limited
Date: 2014
DOI: 10.3402/PBA.V4.23866
Publisher: MDPI AG
Date: 30-01-2023
DOI: 10.20944/PREPRINTS202301.0515.V2
Abstract: Cells produce reactive oxygen species (ROS) as by-products of metabolism, which can give rise to a two-sided effect on the body under balanced and imbalanced oxidant homeostasis conditions. Antioxidant supplements exert their beneficial efficacy in the treatment of metabolic diseases only when the oxidant homeostasis is imbalanced with the over-production of ROS. Over-supplementation of antioxidant(s) can also cause an imbalanced oxidant homeostasis to exert detriments to the induction of metabolic diseases. This commentary raises a concern that prior to precise supplementation of antioxidants, an establishment of oxidant homeostasis status is required in avoiding an imbalanced oxidant homeostasis in vivo. In searching for valid oxidant stress makers, 3-Nitrotyrosine seems to fit in with the selection criteria and its quantification can be correlated with the degree of oxidative stress in vivo.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 10-2006
Publisher: Informa UK Limited
Date: 1994
DOI: 10.3109/02713689408995781
Abstract: The interaction of human and bovine alpha-crystallins with bovine lens membranes was evaluated using binding curves and Scatchard plots constructed from scans of SDS-PAGE gels and/or from the association of [14C]-leu alpha-crystallin with the membranes. No differences were observed for total bovine, normal human 19 and 88 year old and cataractous alpha-crystallins. In each case, interaction takes place through two distinct processes, a) a high affinity (Kd = 1 x 10(-8) M) binding with low capacity (25 mg alpha-crystallin/g membrane protein) and b) partitioning (Kp = 0.25 l/g membrane protein). Loss of the high-affinity binding component was observed for bovine nuclear alpha-crystallin. Contrary to previous reports, it is concluded that cataract formation does not affect the ability of human alpha-crystallins to interact with bovine lens membranes. Reanalysis of previously published data supports this conclusion.
Publisher: Public Library of Science (PLoS)
Date: 02-05-2013
Publisher: Elsevier BV
Date: 06-2005
DOI: 10.1016/J.HLC.2005.01.006
Abstract: This study retrospectively examined a consecutive series of patient CKMB s les for a relationship between age (242 subjects, aged from 20 to 96 years old), serum CKMB activity and corresponding mass results analyzed for CKMB-specific activity (activity per molecule, unit/mg). Patients were categorized into six age groups. The means for specific activity of CKMB, standard error and 95% confidence intervals of each group were calculated. CKMB-specific activity in human serum increases with age regardless of gender or MI severity. As this greater propensity for increased CKMB activity may be due to alteration in part due to protein modification of post-MI release in the blood circulation, these findings add further weight for the current move to the use of troponins and other markers of myocardial injury.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 10-2006
Publisher: S. Karger AG
Date: 1997
DOI: 10.1159/000139539
Abstract: This study compares the human plasma protein binding characteristics of MX2 and epirubicin. The binding characteristics were determined by equilibrium dialysis at various concentrations of the drugs. The binding dissociation constant (Kd), binding capacity (Bmax) and partitioning constant (Kp) were obtained by Scatchard analysis of the free and bound drugs in the dialysis compartments. Our results have demonstrated that plasma protein binds epirubicin or MX2 in an unsaturable appearance over the concentration up to 150 mumol/l. At the same concentrations, plasma protein binds more epirubicin than MX2. The nature of the interaction may consist of two classes of specific binding, and a partitioning. The binding dissociation constants were 18 and 17.5 mumol/l for the higher binding class (Kd1) and 315.8 and 316.9 mumol/l for the lower binding class (Kd2), respectively, for epirubicin and MX2. The respective maximum binding capacities (Bmax) of plasma protein for epirubicin and MX2 were significantly different, 0.045 and 0.029 mumol/g protein for the higher binding class (Bmax1), and 0.39 and 0.29 mumol/g protein for the lower binding class (Bmax2). The partitioning constants (Kp) were 21.5 x 10(-5) and 20 x 10(-5) litres/g protein for epirubicin and MX2, respectively. The results suggest that plasma protein binds epirubicin or MX2 with a similar affinity, but has less binding sites for MX2. One contributing mechanism to the difference in activity noted between epirubicin and MX2 may be changes in free drug fractions.
Publisher: Elsevier BV
Date: 2008
Publisher: Elsevier BV
Date: 03-2004
Publisher: Elsevier BV
Date: 10-2019
DOI: 10.1016/J.CCA.2019.07.029
Abstract: Blood s le hemolysis affects pre-analytical quality and may cause pseudohyperkalemia. We established a statistical model to estimate the corrected potassium (K Serum K The final model selected H index, hemoglobin concentration (HGB), and hematocrit (HCT) as important predictors in estimating the K In vitro hemolysis induced pseudohyperkalemia could be accurately predicted and restored by our model for clinical application.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-2006
DOI: 10.1161/01.HYP.0000231509.27406.42
Abstract: Endothelial dysfunction is a hallmark of cardiovascular disease, and the l -arginine:NO pathway plays a critical role in determining endothelial function. Recent studies suggest that smoking, a well-recognized risk factor for vascular disease, may interfere with l -arginine and NO metabolism however, this remains poorly characterized. Accordingly, we performed a series of complementary in vivo and in vitro studies to elucidate the mechanism by which cigarette smoke adversely affects endothelial function. In current smokers, plasma levels of asymmetrical dimethyl-arginine (ADMA) were 80% higher ( P =0.01) than nonsmokers, whereas citrulline (17% P .05) and N-hydroxy- l -arginine (34% P .05) were significantly lower. Exposure to 10% cigarette smoke extract (CSE) significantly affected endothelial arginine metabolism with reductions in the intracellular content of citrulline (81%), N-hydroxy- l -arginine (57%), and arginine (23%), while increasing ADMA (129%). CSE significantly inhibited (38%) arginine uptake in conjunction with a 34% reduction in expression of the arginine transporter, CAT1. In conjunction with these studies, CSE significantly reduced the activity of eNOS and NO production by endothelial cells, while stimulating the production of reactive oxygen species. In conclusion, cigarette smoke adversely affects the endothelial l -arginine NO synthase pathway, resulting in reducing NO production and elevated oxidative stress. In conjunction, exposure to cigarette smoke increases ADMA concentration, the latter being a risk factor for cardiovascular disease.
Publisher: Wiley
Date: 2007
DOI: 10.1002/BMC.750
Abstract: Oxidative stress plays an important role in pathogenesis of many diseases. Measurement of 3-nitrotyrosine (NO(2)Tyr), as a potential biomarker for nitric oxide-mediated damage, has recently been the focus of particular attention. We have developed an HPLC method with NBD-F pre-column derivatization followed by C(18) cartridge cleaning. Using this method we achieved limits of detection of 0.5 and 1.1 nm for NO(2)Tyr and tyrosine (Tyr), respectively, close to that achieved by LS-MS/MS. NO(2)Tyr and tyrosine concentrations were linear over the calibration ranges 0.5-100 nm and 1-320 microm, respectively, with correlation coefficients greater than 0.95. To evaluate the utility of this assay in plasma we analysed s les obtained from smokers and non-smoking subjects. Consistent with the presence of elevated oxidative stress, the plasma NO(2)Tyr concentration and NO(2)Tyr:Tyr ratio of smokers were 17.42 +/- 11.6 nm and 0.263 +/- 0.192 nm/microm with 3.8 and 3.9 times higher (both p < 0.05), respectively, than that of non-smoker controls (4.54 +/- 2.75 nm and 0.067 +/- 0.050 nm/microm, respectively). In conclusion, we have developed a novel HPLC assay for NO(2)Tyr without MS detection that is applicable to clinical studies addressing the pathophysiology and importance of oxidative stress.
Publisher: MDPI AG
Date: 14-02-2021
DOI: 10.3390/BIOM11020280
Abstract: Hyperuricemia is a risk factor for gout. It has been well observed that a large proportion of in iduals with hyperuricemia have never had a gout flare(s), while some patients with gout can have a normuricemia. This raises a puzzle of the real role of serum uric acid (SUA) in the occurrence of gout flares. As the molecule of uric acid has its dual effects in vivo with antioxidant properties as well as being an inflammatory promoter, it has been placed in a delicate position in balancing metabolisms. Gout seems to be a multifactorial metabolic disease and its pathogenesis should not rely solely on hyperuricemia or monosodium urate (MSU) crystals. This critical review aims to unfold the mechanisms of the SUA role participating in gout development. It also discusses some key elements which are prerequisites for the formation of gout in association with the current therapeutic regime. The compilation should be helpful in precisely fighting for a cure of gout clinically and pharmaceutically.
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