Defective superoxide-dismutase molecules accumulate with age in human lenses
ABSTRACT The specific activity of superoxide dismutase (SOD) in human transparent lenses declines as a function of age. Immunotitration using monospecific antibodies showed that, with increasing age, lenses exhibit an accumulation of catalytically inactive, but antigenically reactive, enzyme molecules. Antiserum produced against denatured enzyme removed the inactive molecules from the lens homogenates without affecting the enzyme activity. These aberrant molecules are at least partially denatured and are totally devoid of catalytic activity.
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- "In the case of a crystallin, one notable feature of the sequences of two of the most abundant peptides (aA 67–80 and aB 1–18) was that sites of cleavage were adjacent to Ser residues (Santhoshkumar et al. 2008; Su et al. 2010). Since enzyme activity is absent in the nuclei of adult human lenses (Scharf et al. 1987; Charlton and van Heyningen 1971; Dovrat et al. 1984; Zhu et al. 2010), we investigated whether such cleavages may result from spontaneous reactions involving Ser. In this study a peptide that encompasses the sequence of the cleavage site in aB crystallin (aB 16-21 Fig. 1) was incubated at neutral pH and the products characterised. "
ABSTRACT: Long-lived proteins are found at several sites in the body and they undergo numerous changes as a result of prolonged exposure to physiological conditions. Truncation is a common modification and many cleavages appear to be non-enzymatic, however little is known about the processes involved. In this study we demonstrate, using synthetic peptides that incorporate the sequence of a protein that is known to cleave in older lenses, that truncation on the N-terminal side of serine residues can occur at neutral pH. A mechanism that incorporates an N,O-acyl shift, which is analogous to intein cleavage, is proposed. Such cleavages may explain the origin of abundant peptides derived from crystallins in aged human lenses. KeywordsOld proteins–Age–Hydrolysis–Posttranslational modification–Human lensInternational Journal of Peptide Research and Therapeutics 06/2011; 17(2):131-135. DOI:10.1007/s10989-011-9250-3 · 0.83 Impact Factor
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ABSTRACT: Lipid peroxidation was shown to be an initiatory cause of cataract development in some cases. It has been established that injection into the vitreous body of the rabbit eye of a suspension of liposomes prepared from phospholipids containing lipid peroxidation products induces the development of posterior subcapsular cataract. Such modelling of cataract is based on a type of clouding of the crystalline lens similar to that observed in cataract resulting from diffusion of toxic lipid peroxidation products from the retina to the lens through the vitreous body on degeneration of the photoreceptors. Saturated liposomes (prepared from dipalmitoylphosphatidylcholine) did not cause clouding of the lens, which demonstrated the peroxide mechanism of the genesis of this form of cataract. Clouding of the lens was accompanied by accumulation of fluorescing lipid peroxidation products in the vitreous body, aqueous humor and the lens and also by a fall in the concentration of reduced glutathione in the lens. The ability of L-carnosine (beta-alanyl-L-histidine) to interact directly with lipid peroxidation products suggested its anticataract properties. The effect of L-carnosine on inhibiting or reversing the formation of cataract induced by the administration of lipid peroxidation products was discovered. This phenomenon appeared to be related with normalization of the peroxide metabolism parameters in the crystalline lens. In view of the data, an aqueous solution of L-carnosine is physiologically acceptable in effective nonsurgical treatment of cataracts.Biochimica et Biophysica Acta 09/1989; 1004(3):363-71. DOI:10.1016/0005-2760(89)90085-4 · 4.66 Impact Factor
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ABSTRACT: Aqueous humor and lenses from cataractous patients of cortical, nuclear and brunescent types of different age groups from males and females were analysed for their contents of H2O2 MDA, Ca and isoelectric points. The regulation of calcium (in vivo) were studied by using Vit. D., calcitonin and parathyroid hormone. Significant enhancement of H2O2, MDA and Ca was observed in human cataractous lenses and aqueous humor. In vivo studies indicate that any alteration/deviation in Vit.D, calcitonin and parathyroid hormone homeostasis may induce hypo/hypercalcemia and hypo/hyperphosphatemia. The combined effect of these biochemical parameters can lead to damage of ocular tissues.Journal of environmental science and health. Part A, Environmental science and engineering & toxic and hazardous substance control 07/1992; 27(5):1273-1292. DOI:10.1080/10934529209375796