Lipids in Health and Disease | |
Imbalance in superoxide dismutase/thioredoxin reductase activities in hypercholesterolemic subjects: relationship with low density lipoprotein oxidation | |
Tatiana Emanuelli2  Marta Medeiros Frescura Duarte1  Juliana Tanara Vicentini2  Greicy Michelle Marafiga Conterato2  Sabrina Somacal2  Andréia Quatrin2  Amanda Roggia Ruviaro2  Paula Rossini Augusti3  | |
[1] Departament of Health Sciences, Lutheran University of Brazil, Santa Maria, RS, Brazil;Department of Food Technology and Science, Integrated Center for Laboratory Analysis Development (NIDAL), Center of Rural Sciences, Federal University of Santa Maria, Santa Maria, RS, Brazil;Campus Itaqui, Federal University of Pampa, Itaqui, RS, Brazil | |
关键词: Thioredoxin reductase; Superoxide dismutase; Oxidized low density lipoprotein; Hypercholesterolemia; Atherogenic index; | |
Others : 1160269 DOI : 10.1186/1476-511X-11-79 |
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received in 2012-04-24, accepted in 2012-06-09, 发布年份 2012 | |
【 摘 要 】
Background
There is a relationship among hypercholesterolemia, oxidative stress and inflammation in the atherogenesis. Thus, the objective of the present study was to assess paraoxonase (PON1), superoxide dismutase (SOD) and thioredoxin reductase (TrxR-1) activities and their relationship with lipids, oxidative stress and inflammation in subjects with different low density lipoprotein-cholesterol (LDL) levels.
Methods
Serum lipids, highly sensitive C-reactive protein (hs-CRP), lipid and protein oxidation, oxidized LDL (LDLox) and LDLox autoantibodies (LDLoxAB) levels and enzymes activities were measured in a total of 116 subjects that were divided into the following groups according to their LDL levels: low-LDL group (LDL < 100 mg/dL, n = 23), intermediate-LDL group (LDL 100–160 mg/dL, n = 50) and high-LDL group (LDL > 160 mg/dL, n = 43).
Results
The LDLox and hs-CRP levels increased in the high-LDL group (2.7- and 3.7- fold, respectively), whereas the intermediate and high-LDL groups had higher LDLoxAB (2.2- and 3.1-fold) when compared to low-LDL group (p < 0.05). Similarly, SOD activity, the atherogenic index (AI) and protein oxidation were also higher in the intermediate (1.3-, 1.3- and 1.2-fold) and high-LDL (1.6-, 2.3- and 1.6-fold) groups when compared to the low-LDL group (p < 0.05). Lipid oxidation and SOD/TrxR-1 ratio increased only in the high-LDL group (1.3- and 1.6-fold) when compared to the low-LDL group (p < 0.05). The SOD/TrxR-1 ratio was positively correlated to TBARS (r = 0.23, p < 0.05), LDLox (r = 0.18, p < 0.05), LDLoxAB (r = 0.21, p < 0.05), LDL (r = 0.19, p < 0.05) and AI (r = 0.22, p < 0.05). PON1 and TrxR-1 activities were similar among groups.
Conclusions
Some oxidative events initiate when LDL levels are clinically acceptable. Moreover, hypercholesterolemic patients have an imbalance in SOD and TrxR-1 activities that is positively associated to LDL oxidation.
【 授权许可】
2012 Augusti et al.; licensee BioMed Central Ltd.
【 预 览 】
Files | Size | Format | View |
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20150410100938697.pdf | 468KB | download | |
Figure 2. | 32KB | Image | download |
Figure 1. | 28KB | Image | download |
【 图 表 】
Figure 1.
Figure 2.
【 参考文献 】
- [1]Steinberg D, Gotto AM: Preventing coronary artery disease by lowering cholesterol levels: fifty years from bench to bedside. J Am Med Ass 1999, 282:2043-2050.
- [2]Batlouni M: Hipótese oxidativa da aterosclerose. Arq Bras Cardiol 1997, 68:55-63.
- [3]Packard RRS, Libby P: Inflammation in atherosclerosis: from vascular biology to biomarker discovery and risk prediction. Clin Chem 2008, 54:24-38.
- [4]Aviram M, Rosenblat M, Bisgaier CL, Newton RS, Primo-Parmo SL, La Du BN: Paraoxonase inhibits high-density lipoprotein oxidation and preserves its functions. A possible peroxidative role for paraoxonase. J Clin Invest 1998, 101:1581-1590.
- [5]Aviram M: Does paraoxonase play a role in susceptibility to cardiovascular disease?Mol. Med Today 1999, 5:381-386.
- [6]Cai H, Harrison DG: Endothelial dysfunction in cardiovascular diseases: the role of oxidant stress. Circ Res 2000, 87:840-844.
- [7]Stralin P, Karlsson K, Johansson BO, Marklund SL: The interstitium of the human arterial wall contains very large amounts of extracellular superoxide dismutase. Arterioscler Thromb Vasc Biol 1995, 15:2032-2036.
- [8]Arnér ESJ, Holmgren A: Physiological functions of thioredoxin and thioredoxin reductase. Eur J Biochem 2000, 267:6102-6109.
- [9]Söderberg A, Sahaf B, Rosén A: Thioredoxine reductase, a redoxactive selenoprotein, is secreted by normal and neoplastic cells: presence in human plasma. Cancer Res 2000, 60:2281-2289.
- [10]Kunihisa M, Chiharu K, Nakamura H, Makita T, Ishii K, Okuda N, Yodoi J, Sasayama S: Serum thioredoxin and α-tocopherol concentrations in patients with major risk factors. Circ J 2005, 69:291-294.
- [11]Kishimoto C, Shioji K, Nakamura H, Nakayama Y, Yodoi J, Sasayama S: Serum thioredoxin (TRX) levels in patients with heart failure. Jpn Circ J 2001, 65:491-494.
- [12]Wu Y, Yang L, Zhong L: Decreased serum levels of thioredoxin in patients with coronary artery disease plus hyperhomocysteinemia is strongly associated with the disease severity. Atherosclerosis 2010, 212:351-355.
- [13]Jekell A, Hossain A, Alehagen U, Dahlström U, Rose’ A: Elevated circulating levels of thioredoxin and stress in chronic heart failure. Eur J Heart Fail 2004, 6:883-890.
- [14]Augusti PR, Conterato GMM, Somacal S, Sobieski R, Quatrin A, Maurer L, Rocha MP, Denardin IT, Emanuelli T: Astaxanthin reduces oxidative stress, but not aortic damage in atherosclerotic rabbits. J Cardiovasc Pharmacol Ther 2009, 14:314-322.
- [15]Fassini PG, Noda RW, Ferreira ES, Silva MA, Neves VA, Demonte A: Soybean glycinin improves HDL-C and suppresses the effects of rosuvastatin on hypercholesterolemic rats. Lipid Health Dis 2011, 10:165. BioMed Central Full Text
- [16]Witztum JL, Steinbrecher UP, Fisher M, Kesaniemi A: Nonenzymatic glucosylation of homologous LDL and albumin render them inununogenic in the guinea pig. Proc Natl Acad Set U S A 1983, 80:2757-2761.
- [17]Steinbrecher UP, Fisher M, Witztum JL, Curtiss LK: Immunogenicity of homologous low density lipoprotein after methylation, ethylation, acetylation or carbamylation: generation of antibodies specific for derivatized lysine. Lipid Res 1984, 25:1109-1116.
- [18]Wiklund O, Witztum JL, Carew TE, Pittman RC, Elam RL, Steinberget D: Turnover and tissue sites of degradation of glucosylated low density lipoprotein in normal and immunized rabbits. J Lipid Res 1987, 28:1098-1109.
- [19]Shoji T, Nishizawa Y, Fukumoto M, Shimamura K, Kimura J, Kanda H, Emoto M, Kawagishi T, Morii H: Inverse relationship between circulating oxidized low density lipoprotein (oxLDL) and anti-oxLDL antibody levels in healthy subjects. Atherosclerosis 2000, 148:171-177.
- [20]Yla-Herttuala S, Palinski W, Butler SW, Picard S, Steinberg D, Witztum JL: Rabbit and human atherosclerotic lesions contain IgG that recognizes epitopes of oxidized LDL. Arterioscler Thromb Vasc Biol 1994, 14:32-40.
- [21]Ohara Y, Peterson TE, Harrison DG: Hypercholesterolemia increases endothelial superoxide anion production. J Clin Invest 1993, 91:2546-2551.
- [22]Augusti PR, Quatrin A, Somacal S, Conterato GMM, Sobieski R, Ruviaro AR, Maurer LH, Duarte MMF, Roehrs M, Emanuelli T: Astaxanthin prevents changes in the activities of thioredoxin reductase and paraoxonase in hypercholesterolemic rabbits. J Clin Biochem Nutrin press
- [23]Bambini-Junior V, Rodrigues L, Behr GA, Moreira JCF, Riesgo R, Gottfried C: Animal model of autism induced by prenatal exposure to valproate: behavioral changes and liver parameters. Brain Res 2011, 1408:8-16.
- [24]Pinho RA, Andrades ME, Oliveira MR, Pirola AC, Zago MS, Silveira PCL, Dal-Pizzol F, Moreira JCF: Imbalance in SOD/CAT activities in rat skeletal muscles submitted to treadmill training exercise. Cell Biol Int 2006, 30:848-853.
- [25]Mackness B, Durrington P, McElduff P, Yarnell J, Azam N, Watt M, Mackness M: Low paraoxonase activity predicts coronary events in the Caerphilly prospective study. Circulation 2003, 107:2775-2779.
- [26]Aviram M, Rosenblat M, Billecke S, Erogul J, Sorenson R, Bisgaier CL, Newton RS, La Du B: Human serum paraoxonase (PON 1) is inactivated by oxidized low density lipoprotein and preserved by antioxidants. Free Rad Biol Med 1999, 26:892-904.
- [27]Mackness B, Hunt R, Durrington PN, Mackness MI: Increased immunolocalization of paraoxonase, clusterin, and apolipoprotein A-I in the human artery wall with the progression of atherosclerosis. Arterioscler Thromb Vasc Biol 1997, 17:1233-1238.
- [28]Jayakumari N, Thejaseebai G: High prevalence of low serum paraoxonase-1 in subjects with coronary artery disease. J Clin Biochem Nutr 2009, 45:278-284.
- [29]Van Himbergen TM, Roest M, de Graaf J, Jansen EH, Hattori H, Kastelein JJ, Voorbij HA, Stalenhoef AF, Van Tits LJ: Indications that paraoxonase-1 contributes to plasma high density lipoprotein levels in familial hypercholesterolemia. J Lipid Res 2005, 46:445-451.
- [30]Lemarechal H, Allanore Y, Chenevier-Gobeaux C, Ekindjian OG, Kahan A, Borderie D: High redox thioredoxin but low thioredoxin reductase activities in the serum of patients with rheumatoid arthritis. Clin Chim Acta 2006, 367:156-161.
- [31]Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults: Executive summary of the third report the National Cholesterol Education Program (Adults Treatment III). JAMA 2001, 285:2486-2497.
- [32]Bachorik PS, Albers JJ: Precipitation methods for quantification of lipoproteins. Methods Enzymol 1996, 129:78-100.
- [33]Friedewald WT, Levy RI, Fredrickson DS: Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without the use of preparative ultracentrifuge. Clin Chem 1972, 18:499-502.
- [34]Yang R, Shi Y, Hao G, Li W, Le G: Increasing oxidative stress with progressive hyperlipidemia in human: relation between malondialdehyde and atherogenic index. J Clin Biochem Nutr 2008, 43:154-158.
- [35]Holvoet P, Stassen JM, Van Cleemput J, Collen D, Vanhaecke J: Oxidized low density lipoproteins in patients with transplant-associated coronary artery disease. Arterioscler Thromb Vasc Biol 1998, 18:100-107.
- [36]Wu R, Lefvert AK: Autoantibodies against oxidized low density lipoprotein (OxLDL): characterization of antibody isotype, subclass, affinity and effect on the macrophage uptake of oxLDL. Clin Exp Immunol 1995, 102:174-180.
- [37]Ohkawa H, Ohishi N, Yagi K: Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 1979, 95:351-358.
- [38]Levine RL, Garland D, Oliver CN, Amici A, Climent I, Lenz AG, Ahn BW, Shaltiel S, Stadtman ER: Determination of carbonyl content in oxidatively modified proteins. Method Enzymol 1990, 186:464-478.
- [39]Misra HP, Fridovich I: The role of superoxide anion in the auto-oxidation of epinephrine and a simple assay for superoxide-dismutase. J Biol Chem 1972, 247:3170-3175.
- [40]Holmgren A, Björnstedt M: Thioredoxin and thioredoxin reductase. Meth Enzymol 1995, 252:199-208.
- [41]Bolayirli IM, Aslan M, Balci H, Altug T, Hacibekiroglu M, Seven A: Effects of atorvastatin therapy on hypercholesterolemic rabbits with respect to oxidative stress, nitric oxide pathway and homocysteine. Life Sci 2007, 81:121-127.