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.
"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. "
[Show abstract][Hide abstract] 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 lens
International Journal of Peptide Research and Therapeutics 06/2011; 17(2):131-135. DOI:10.1007/s10989-011-9250-3 · 0.91 Impact Factor
[Show abstract][Hide abstract] 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.
[Show abstract][Hide abstract] ABSTRACT: Pulmonary Cu,Zn superoxide dismutase was examined in young (1-month-old), adult (4-5-month-old) and aged (24-months-old) rats to determine if partially inactive forms of the enzyme accumulate in the lung with age. Measurement of Cu,Zn superoxide dismutase activity in lung homogenates showed that total Cu,Zn superoxide dismutase activity/mg DNA was essentially the same in adult and aged rats. The average value of Cu,Zn superoxide dismutase/mg DNA for young rats was less than half that of adult and aged rats. Cu,Zn superoxide dismutase was purified from the lung homogenates and fractionated into isoelectric variants by either isoelectric focusing or chromatofocusing. Three main isoelectric variants of Cu,Zn superoxide dismutase were recovered with pI values of 5.15, 4.88 and 4.75. In all age groups studied, the pI 4.88 variant had a markedly higher specific activity than the other two variants, as well as the highest metal content and greatest resistance to inactivation of all three variants. The pI 4.88 variant declined from 88% of the total Cu,Zn superoxide dismutase activity in the young animals to only 70% in the aged animals. The results of this study indicate that the proportion of the relatively inactive forms of pulmonary Cu,Zn superoxide dismutase increased with age.
Mechanisms of Ageing and Development 04/1990; 52(1):11-26. DOI:10.1016/0047-6374(90)90141-2 · 3.40 Impact Factor
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