Glycation by ascorbic acid oxidation products leads to the aggregation of lens proteins

Linetsky, Mikhail; Shipova, Ekaterina V.; Cheng, Rongzhu; Ortwerth, B.J.

doi:10.1016/j.bbadis.2007.10.003

Cited by 89 publications

(66 citation statements)

References 63 publications

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“…The vast majority of the lens pigments are confined to the water-insoluble protein fraction of the human lens (1,6). The proteins containing these pigments exist as highly cross-linked, large aggregates capable of scattering visible light impinging on the lens (8,9). Although numerous previous studies have attempted to elucidate the biochemical pathways that lead to the formation of these pigments, none so far have succeeded.…”

mentioning

confidence: 97%

UVA Light-excited Kynurenines Oxidize Ascorbate and Modify Lens Proteins through the Formation of Advanced Glycation End Products

Linetsky

Raghavan

Johar³

et al. 2014

Journal of Biological Chemistry

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Background: Human lens proteins accumulate pigmented, protein-cross-linked AGE adducts during cataract formation, and the mechanisms of their formation are poorly understood. Results: UVA-excited kynurenines can oxidize ascorbate under anoxic conditions and promote synthesis of AGEs. Conclusion: UVA light-excited kynurenines promote AGE synthesis and contribute to cataract formation. Significance: This study provides a mechanism for UVA light-mediated damage to lens proteins during cataract formation.

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confidence: 97%

UVA Light-excited Kynurenines Oxidize Ascorbate and Modify Lens Proteins through the Formation of Advanced Glycation End Products

Linetsky

Raghavan

Johar³

et al. 2014

Journal of Biological Chemistry

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“…Ова модификација сочивних кристалина води ка формирању протеинских агрегата, велике молекулске масе, што доприноси развоју катаракте. Неке студије наводе и аскорбат као узрочни фактор ове модификације протеина (139). Аскорбат у неким условима може деловати као прооксиданс и учествовати у стварању реактивних радикала кисеоника.…”

Section: глутатионunclassified

“…Аскорбатом изазвана модификација кристалина сочива може довести до њихове агрегације и преципитације (139).…”

Section: глутатионunclassified

“…Бројне студије су такође, потврдиле низак ниво аскорбинске киселине у катарактним сочивима, смањење нивоа аскорбата у хуманим сочивима са узнапредовалом сенилном катарактом (108) и повећану концентрацију дехидроскорбата (139,218). Већа концентрација дехидроаскорбата у сочивима испитаника оболелих од сенилне катаракте се може објаснити немогућношћу његове редукције у аскорбинску киселину због смањене количине редукованог глутатиона, која је такође измерена у поменутим сочивима (табела 23), о чему је било речи у претходном поглављу.…”

Section: промене концентрације витамина ц у сочиву пацијента са сенилunclassified

“…Могуће је да низак ниво редукованог глутатиона доводи до нагомилавања деградационих продуката аскорбинске киселине (дехидроаскорбинске киселине 2,3-дикетоглуконске киселине, Л-ксилосона (L-xylosone) i Л-треозе (L-threose) у катарактним сочивима. Постоје мишљења да су ови интермедијери потенцијални агенси модификације сочивних протеина, чак и потентнији од глукозе (133) и да модификација кристалина сочива овим продуктима доводи до њихове агрегације и преципитације (139). Експерименти на изолованим протеинима, показују да оксидациони продукти аскорбата могу стварати унакрсне везе са кристалинима сочива, продукујући молекуле велике молекулске масе, који узрокују светлосно расејање карактеристично за катаракту (165).…”

Section: промене концентрације витамина ц у сочиву пацијента са сенилunclassified

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Oxidative stress and antioxidant defense elements in the genesis of cataracts

Kisić¹

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Introduction. The immediate cause for the occurrence of cataract is unknown, but oxidative damage and effects of reactive oxygen species are considered important in its etiopathogenesis. Aim. The study was aimed at testing the products oxidative stress and antioxidant protection factors in serum and corticonuclear lenses blocks of patients with different types and different degrees of maturity of agerelated cataract. Material and Methods. Patients. Clinical and biochemical researches were carried out in 101 patients with age-related cataract, 46 women and 55 men. The average age of the group was 72.5 (SD ± 7.98). According to the cataract maturity degree the patients were classified into two groups as follows: cataract senilis incipiens (N=41) and cataract senilis matura (N=60). Serum samples and corticonuclear lenses blocks were obtained to detect the products of lipid peroxidation: conjugated diene, fluorescent lipid peroxidation products and malondialdehyde and activities antioxidative enzymes: superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and glutathione S-transferase. Results. Significantly higher concentration of diene conjugation in corticonuclear lenses blocks was measured in the patients with cataract senilis incipiens (p<0.001) as well as the intensity of fluorescent iminopropens (p<0.001). Significantly higher concentration of malondialdehyde in corticonuclear lenses blocks (p<0.001) was measured in the patients with cataracta senilis matura. Conclusion. Based on the found lipid peroxidation products measuring results in corticonuclear lenses blocks in the patients with cataract diagnosis, it can be concluded that the lens structure changes caused by lipid peroxidation can, with other risk factors present, influence occurrence and development of cataract. Some cataract types show different lipid peroxidation intensity with the most distinct changes in the cataract wich started as nuclear. Кључне речиОксидациони стрес, катаракта, липидна пероксидација, антиоксидантни ензими.

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External Factors Affecting Protein Aggregation

Wang

Speaker

2010

Aggregation of Therapeutic Proteins

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The behavior of biotherapeutic proteins is signifi cantly different from small molecule drugs both in liquid and solid states, especially in terms of physical stability. One such property is the high tendency of protein molecules to aggregate under a variety of conditions. The aggregation tendency is arguably the most common and troubling manifestation of protein instability during the development of protein biotherapeutics. 1 Protein aggregates usually exhibit either reduced or, in many cases, no biological activity. 2 -5 A clear correlation was established between loss of recombinant factor VIII (rFVIII ) and its degree of aggregation as shown in Fig. 4.1 . 6 To achieve effective prevention or inhibition of protein aggregation, it is of paramount importance to understand all the possible factors that affect or control the protein aggregation process.Many factors have been identifi ed and reported in the literature affecting the process and rate of protein aggregation. These factors can be roughly divided into two major categories: internal (protein structure related) and external (protein environment related). Chapter 3 in this book has focused extensively on factors that belong to the fi rst category. This chapter focuses on the external factors that affect the process and rate of protein aggregation. To facilitate discussion, these external factors are further divided into the following sections: (1) temperature; (2) solution conditions and composition (pH, buffer type and concentration, ionic strength, excipients and level, protein concentration, metal ions, denaturing and reducing agents, impurities, organic solvents, containers/closures, sources of proteins, sample treatment, and analytical methodologies); (3) processing steps (fermentation/expression,

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Glycation by ascorbic acid oxidation products leads to the aggregation of lens proteins

Cited by 89 publications

References 63 publications

UVA Light-excited Kynurenines Oxidize Ascorbate and Modify Lens Proteins through the Formation of Advanced Glycation End Products

UVA Light-excited Kynurenines Oxidize Ascorbate and Modify Lens Proteins through the Formation of Advanced Glycation End Products

Oxidative stress and antioxidant defense elements in the genesis of cataracts

External Factors Affecting Protein Aggregation

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