Oxidative changes in human lens proteins during senile nuclear cataract formation

Truscott, Roger J.W.; Augusteyn, Robert C.

doi:10.1016/0005-2795(77)90212-4

Cited by 227 publications

(110 citation statements)

References 17 publications

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“…These data, in combination with data showing increased Met(O) content in aged and cataract lenses (Spector, 1995;Truscott and Augusteyn, 1977;Garner and Spector, 1980) suggests that loss of MsrA activity in combination with the formation of Met(O) and concomitant loss of mitochondrial function could be important factors in the development of cataract and other oxidative stress associated diseases. Detection of mitochondrial membrane potential in HLE cells treated with MsrA-specific siRNAs in the absence of oxidative stress.…”

Section: Discussionmentioning

confidence: 52%

“…Met(O) is barely detectable in young lenses but increases in the lens with age (Spector, 1995) suggesting that Met(O) formation is a characteristic of lens aging. In cataract, as much as 60% of membrane bound protein methionines are found as Met(O) (Truscott and Augusteyn, 1977;Garner and Spector, 1980) providing an association between methionine oxidation and cataract development. Met(O) formation is known to cause loss of protein and subsequent cellular function (Brot et al, 1981;Caldwell et al, 1978;Ciorba et al, 1997;Johnson and Travis, 1979;Vogt, 1995;Swaim and Pizzo, 1988) that could be detrimental to lens homeostasis and be a causative factor in cataract formation.…”

Section: Introductionmentioning

confidence: 99%

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Silencing of the methionine sulfoxide reductase A gene results in loss of mitochondrial membrane potential and increased ROS production in human lens cells

Marchetti

Lee

Cowell

et al. 2006

Experimental Eye Research

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Accumulation of methionine sulfoxide (Met(O)) is a significant feature of human cataract and previous studies have shown that methionine sulfoxide reductase A (MsrA), which acts to repair Met (O), can defend human lens cells against oxidative stress induced cell death. A key feature of oxidative stress is increased reactive oxygen species (ROS) in association with loss of mitochondrial function. Here, we sought to establish a potential role for MsrA in the accumulation of ROS in lens cells and the corresponding mitochondrial membrane potential in these cells. Targeted gene silencing was used to establish populations of lens cells expressing different levels of MsrA, and the mitochondrial membrane potential and ROS levels of these cell populations were monitored. Decreased MsrA levels were found to be associated with loss of cell viability, decreased mitochondrial membrane potential, and increased ROS levels in the absence of oxidative stress. These effects were augmented upon oxidative stress treatment. These results provide evidence that MsrA is a major determinant for accumulation of ROS in lens cells and that increased ROS levels in lens cells are associated with a corresponding decrease in mitochondrial membrane potential that is likely related to the requirement for MsrA in lens cell viability.

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Section: Discussionmentioning

confidence: 52%

Section: Introductionmentioning

confidence: 99%

Silencing of the methionine sulfoxide reductase A gene results in loss of mitochondrial membrane potential and increased ROS production in human lens cells

Marchetti

Lee

Cowell

et al. 2006

Experimental Eye Research

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“…It is thought that when the level of GSH drops below 1mM in the lens nucleus, PSSP formation and eventual nuclear cataract is initiated. More than 90% of -SH groups in the human lens are oxidized to -SS-in mature nuclear cataracts (Truscott and Augusteyn, 1977;Garner and Spector, 1980). A substantial loss of -SH was observed in the O 2 -treated lens nucleus compared to age-matched controls at both 50 and 85 treatments with HBO (Fig.…”

Section: Discussionmentioning

confidence: 87%

Raman spectroscopic evidence for nuclear disulfide in isolated lenses of hyperbaric oxygen-treated guinea pigs

Gosselin

Kapustij

Venkateswaran

et al. 2007

Experimental Eye Research

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Our laboratory treats guinea pigs with hyperbaric oxygen (HBO) as a model for investigating the formation of nuclear cataract. Previous analyses of lens supernatants using this model have shown an increase in disulfide (-SS-) and loss of sulfhydryl (-SH) in the lens nucleus of O 2 -treated animals. In this paper, we have used the non-invasive technique of Raman spectroscopy to confirm these findings in intact, freshly-excised lenses. Guinea pigs were treated 3 times per week with HBO for a total of 50 (4 months of treatment) or 85 (7 months of treatment) times to induce an increased level of lens nuclear light scattering. Intact lenses were analyzed by Raman spectroscopy using a 514.5 nm laser and collecting the scattered light in a 90° geometry. The laser beam was focused either in the lens nucleus or equatorial cortex. Changes in the levels of -SS-(503 cm −1 ) and -SH (2577 cm −1 ) vibrations were measured. Raman spectra were analyzed by fitting Lorentzian profiles to the observed data in the -SS-and -SH regions. -SS-levels in the O 2 -treated nucleus were found to have increased by a factor of 2.1 (p=0.0001) and 2.5 (p=0.001) after 50 and 85 HBO treatments, respectively, compared to age-matched controls. Based on previous biochemical analyses, the -SSincrease was due mainly to the formation of protein disulfide (PSSP) with contribution also from protein/thiol mixed disulfides, but not from oxidized glutathione. -SH levels in the O 2 -treated nucleus decreased by 13% (p=0.007) and 35% (p=0.001) after 50 and 85 HBO treatments, respectively, compared to age-matched controls. No significant increase in -SS-or loss of -SH was observed in the lens cortex of the O 2 -treated guinea pigs. The Raman spectroscopy results rule out the possibility that artifactual production of -SS-and loss of -SH occurred during homogenization of lenses in previous studies. The data provide additional evidence to support a link between O 2 , disulfidecrosslinking of lens crystallins in the nucleus, and nuclear cataract.

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“…Although modern techniques for cataract surgery are available in Pakistan now, because of less availability, the classical surgical procedures for removal of eye lenses are used, and the sample collection of mature and hyper mature eye lenses in intact form was possible. Different biochemical changes occur during cataract surgery e.g., an increase in the amount of insoluble protein, cross-linked protein, oxidised cysteine in the protein, oxidised methionine in the protein (Truscott and Augusteyn, 1977a;1977b;1977c), protein amino acids which have been modified by hydroxyl radical, and a decrease in the amount of the antioxidant glutathione in the centre of the lens (Truscott and Augusteyn, 1977a;1977b;1977c). Proteases are reported to be involved in the development of cataract (Sulochana et al, 1996;Sharma and Ortwerth, 1986).…”

Section: Introductionmentioning

confidence: 99%

Comparison in effect of different metal ions, pH and reducing agent on the protease activity in human hyper mature and mature cataract

Sami

Kanwal

2007

J. Zhejiang Univ. - Sci. B

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This study was undertaken to isolate and characterize the protease activity of human eye lens sample of mature and hyper mature cataract. Samples were collected just after surgery of the cataract lens and were stored at −20 °C. The total protein extract was isolated from 5 samples in each case (mature and hyper mature cataract) and clear supernatant obtained after centrifugation was used as an enzyme source. The optimum pH for the proteases of mature cataract was 7.5 while the proteases of hyper mature cataract were recorded for maximum activity at pH 5.5 and 7.5. The optimum temperature for both enzyme sources was 50 °C. Effect of different metal ions such as potassium, lead, silver, zinc and borate was studied. In each case protease activity was increased. Reducing agent e.g. β mercaptoethanol also caused an increase in activity indicating the involvement of sulfhydryl groups. Protease activity was also located on agar plates.

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Oxidative changes in human lens proteins during senile nuclear cataract formation

Cited by 227 publications

References 17 publications

Silencing of the methionine sulfoxide reductase A gene results in loss of mitochondrial membrane potential and increased ROS production in human lens cells

Silencing of the methionine sulfoxide reductase A gene results in loss of mitochondrial membrane potential and increased ROS production in human lens cells

Raman spectroscopic evidence for nuclear disulfide in isolated lenses of hyperbaric oxygen-treated guinea pigs

Comparison in effect of different metal ions, pH and reducing agent on the protease activity in human hyper mature and mature cataract

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